LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article ; Online: Inclusion of High-Field Target Data in AMOEBA's Calibration Improves Predictions of Protein-Ion Interactions.

Delgado, Julián A / Wineman-Fisher, Vered / Pandit, Sagar / Varma, Sameer

Journal of chemical information and modeling

2022 Volume 62, Issue 19, Page(s) 4713–4726

Abstract: The reliability of molecular mechanics simulations to predict effects of ion binding to proteins depends on their ability to simultaneously describe ion-protein, ion-water, and protein-water interactions. Force fields (FFs) to describe protein-water and ... ...

Abstract	The reliability of molecular mechanics simulations to predict effects of ion binding to proteins depends on their ability to simultaneously describe ion-protein, ion-water, and protein-water interactions. Force fields (FFs) to describe protein-water and ion-water interactions have been constructed carefully and have also been refined routinely to improve accuracy. Descriptions for ion-protein interactions have also been refined, although in an
MeSH term(s)	Amoeba ; Calibration ; Ions ; Proteins/chemistry ; Reproducibility of Results ; Thermodynamics ; Water/chemistry
Chemical Substances	Ions ; Proteins ; Water (059QF0KO0R)
Language	English
Publishing date	2022-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.2c00758
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1230: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: High-Dimensional Parameter Search Method to Determine Force Field Mixing Terms in Molecular Simulations

Saunders, Matthew / Wineman-Fisher, Vered / Jakobsson, Eric / Varma, Sameer / Pandit, Sagar A.

Langmuir. 2022 Feb. 22, v. 38, no. 9

2022

Abstract: Molecular dynamics (MD) force fields for lipids and ions are typically developed independently of one another. In simulations consisting of both lipids and ions, lipid–ion interaction energies are estimated using a predefined set of mixing rules for ... ...

Abstract	Molecular dynamics (MD) force fields for lipids and ions are typically developed independently of one another. In simulations consisting of both lipids and ions, lipid–ion interaction energies are estimated using a predefined set of mixing rules for Lennard-Jones (LJ) interactions. This, however, does not guarantee their reliability. In fact, compared to the quantum mechanical reference data, Lorentz–Berthelot mixing rules substantially underestimate the binding energies of Na⁺ ions with small-molecule analogues of lipid headgroups, yielding errors on the order of 80 and 130 kJ/mol, respectively, for methyl acetate and diethyl phosphate. Previously, errors associated with mixing force fields have been reduced using approaches such as “NB-fix” in which LJ interactions are computed using explicit cross terms rather than those from mixing rules. Building on this idea, we derive explicit lipid–ion cross terms that also may implicitly include many-body cooperativity effects. Additionally, to account for the interdependency between cross terms, we optimize all cross terms simultaneously by performing high-dimensional searches using our ParOpt software. The cross terms we obtain reduce the errors due to mixing rules to below 10 kJ/mol. MD simulation of the lipid bilayer conducted using these optimized cross terms resolves the structural discrepancies between our previous simulations and small-angle X-ray and neutron scattering experiments. These results demonstrate that simulations of lipid bilayers with ions that are accurate up to structural data from scattering experiments can be performed without explicit polarization terms. However, it is worth noting that such NB-fix cross terms are not based on any physical principle; a polarizable lipid model would be more realistic and is still desired. Our approach is generic and can be applied to improve the accuracies of simulations employing mixed force fields.
Keywords	acetates ; computer software ; lipid bilayers ; lipids ; models ; molecular dynamics ; neutrons ; phosphates ; quantum mechanics ; small-angle X-ray scattering
Language	English
Dates of publication	2022-0222
Size	p. 2840-2851.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.1c03105
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Article ; Online: High-Dimensional Parameter Search Method to Determine Force Field Mixing Terms in Molecular Simulations.

Saunders, Matthew / Wineman-Fisher, Vered / Jakobsson, Eric / Varma, Sameer / Pandit, Sagar A

Langmuir : the ACS journal of surfaces and colloids

2022 Volume 38, Issue 9, Page(s) 2840–2851

Abstract: Molecular dynamics (MD) force fields for lipids and ions are typically developed independently of one another. In simulations consisting of both lipids and ions, lipid-ion interaction energies are estimated using a predefined set of mixing rules for ... ...

Abstract	Molecular dynamics (MD) force fields for lipids and ions are typically developed independently of one another. In simulations consisting of both lipids and ions, lipid-ion interaction energies are estimated using a predefined set of mixing rules for Lennard-Jones (LJ) interactions. This, however, does not guarantee their reliability. In fact, compared to the quantum mechanical reference data, Lorentz-Berthelot mixing rules substantially underestimate the binding energies of Na
MeSH term(s)	Ions/chemistry ; Lipid Bilayers/chemistry ; Molecular Dynamics Simulation ; Reproducibility of Results ; Thermodynamics
Chemical Substances	Ions ; Lipid Bilayers
Language	English
Publishing date	2022-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.1c03105
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Insight into a New Binding Site of Zinc Ions in Fibrillar Amylin.

Wineman-Fisher, Vered / Miller, Yifat

ACS chemical neuroscience

2017 Volume 8, Issue 9, Page(s) 2078–2087

Abstract: Amylin peptides are secreted together with insulin and zinc ions from pancreatic β-cells. Under unknown conditions, the amylin peptides aggregate to produce oligomers and fibrils, and in some cases ... ...

Abstract	Amylin peptides are secreted together with insulin and zinc ions from pancreatic β-cells. Under unknown conditions, the amylin peptides aggregate to produce oligomers and fibrils, and in some cases Zn
MeSH term(s)	Binding Sites ; Cations, Divalent/chemistry ; Cations, Divalent/metabolism ; Humans ; Islet Amyloid Polypeptide/chemistry ; Islet Amyloid Polypeptide/genetics ; Islet Amyloid Polypeptide/metabolism ; Molecular Dynamics Simulation ; Protein Binding ; Protein Conformation ; Zinc/chemistry ; Zinc/metabolism
Chemical Substances	Cations, Divalent ; Islet Amyloid Polypeptide ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2017--20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.7b00221
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Predictive QM/MM Modeling of Modulations in Protein–Protein Binding by Lysine Methylation

Rahman, Sanim / Wineman-Fisher, Vered / Al-Hamdani, Yasmine / Tkatchenko, Alexandre / Varma, Sameer

Journal of molecular biology. 2021 Feb. 05, v. 433, no. 3

2021

Abstract: Lysine methylation is a key regulator of protein–protein binding. The amine group of lysine can accept up to three methyl groups, and experiments show that protein–protein binding free energies are sensitive to the extent of methylation. These ... ...

Abstract	Lysine methylation is a key regulator of protein–protein binding. The amine group of lysine can accept up to three methyl groups, and experiments show that protein–protein binding free energies are sensitive to the extent of methylation. These sensitivities have been rationalized in terms of chemical and structural features present in the binding pockets of methyllysine binding domains. However, understanding their specific roles requires an energetic analysis. Here we propose a theoretical framework to combine quantum and molecular mechanics methods, and compute the effect of methylation on protein–protein binding free energies. The advantages of this approach are that it derives contributions from all local non-trivial effects of methylation on induction, polarizability and dispersion directly from self-consistent electron densities, and at the same time determines contributions from well-characterized hydration effects using a computationally efficient classical mean field method. Limitations of the approach are discussed, and we note that predicted free energies of fourteen out of the sixteen cases agree with experiment. Critical assessment of these cases leads to the following overarching principles that drive methylation-state recognition by protein domains. Methylation typically reduces the pairwise interaction between proteins. This biases binding toward lower methylated states. Simultaneously, however, methylation also makes it easier to partially dehydrate proteins and place them in protein–protein complexes. This latter effect biases binding in favor of higher methylated states. The overall effect of methylation on protein–protein binding depends ultimately on the balance between these two effects, which is observed to be tuned via several combinations of local features.
Keywords	field methods ; lysine ; mechanics ; methylation ; molecular biology
Language	English
Dates of publication	2021-0205
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2020.166745
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 63/108: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Effect of Zn(2+) ions on the assembly of amylin oligomers: insight into the molecular mechanisms.

Wineman-Fisher, Vered / Miller, Yifat

Physical chemistry chemical physics : PCCP

2016 Volume 18, Issue 31, Page(s) 21590–21599

Abstract: Amylin is an endocrine hormone and is a member of the family of amyloid peptides and proteins that emerge as potential scaffolds by self-assembly processes. Zn(2+) ions can bind to amylin peptides to form self-assembled Zn(2+)-amylin oligomers. In the ... ...

Abstract	Amylin is an endocrine hormone and is a member of the family of amyloid peptides and proteins that emerge as potential scaffolds by self-assembly processes. Zn(2+) ions can bind to amylin peptides to form self-assembled Zn(2+)-amylin oligomers. In the current work the binding sites of Zn(2+) ions in the self-assembled amylin oligomers at various concentrations of zinc have been investigated. Our results yield two conclusions. First, in the absence of Zn(2+) ions polymorphic states (i.e. various classes of amylin oligomers) are obtained, but when Zn(2+) ions bind to amylin peptides to form Zn(2+)-amylin oligomers, the polymorphism is decreased, i.e. Zn(2+) ions bind only to specific classes of amylin. At low concentrations of Zn(2+) ions the polymorphism is smaller than at high concentrations. Second, the structural features of the self-assembled amylin oligomers are not affected by the presence of Zn(2+) ions. This study proposes new molecular mechanisms of the self-assembly of Zn(2+)-amylin oligomers.
Language	English
Publishing date	2016-08-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1476244-4
ISSN	1463-9084 ; 1463-9076
ISSN (online)	1463-9084
ISSN	1463-9076
DOI	10.1039/c6cp04105a
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Improved description of ligand polarization enhances transferability of ion-ligand interactions.

Wineman-Fisher, Vered / Al-Hamdani, Yasmine / Nagy, Péter R / Tkatchenko, Alexandre / Varma, Sameer

The Journal of chemical physics

2020 Volume 153, Issue 9, Page(s) 94115

Abstract: The reliability of molecular mechanics (MM) simulations in describing biomolecular ion-driven processes depends on their ability to accurately model interactions of ions simultaneously with water and other biochemical groups. In these models, ion ... ...

Abstract	The reliability of molecular mechanics (MM) simulations in describing biomolecular ion-driven processes depends on their ability to accurately model interactions of ions simultaneously with water and other biochemical groups. In these models, ion descriptors are calibrated against reference data on ion-water interactions, and it is then assumed that these descriptors will also satisfactorily describe interactions of ions with other biochemical ligands. The comparison against the experiment and high-level quantum mechanical data show that this transferability assumption can break down severely. One approach to improve transferability is to assign cross terms or separate sets of non-bonded descriptors for every distinct pair of ion type and its coordinating ligand. Here, we propose an alternative solution that targets an error-source directly and corrects misrepresented physics. In standard model development, ligand descriptors are never calibrated or benchmarked in the high electric fields present near ions. We demonstrate for a representative MM model that when the polarization descriptors of its ligands are improved to respond to both low and high fields, ligand interactions with ions also improve, and transferability errors reduce substantially. In our case, the overall transferability error reduces from 3.3 kcal/mol to 1.8 kcal/mol. These improvements are observed without compromising on the accuracy of low-field interactions of ligands in gas and condensed phases. Reference data for calibration and performance evaluation are taken from the experiment and also obtained systematically from "gold-standard" CCSD(T) in the complete basis set limit, followed by benchmarked vdW-inclusive density functional theory.
MeSH term(s)	Ligands ; Molecular Dynamics Simulation ; Quantum Theory ; Reproducibility of Results ; Thermodynamics
Chemical Substances	Ligands
Language	English
Publishing date	2020-09-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0022058
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Bonn / Germany

Z 4' 49/16: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Predictive QM/MM Modeling of Modulations in Protein-Protein Binding by Lysine Methylation.

Rahman, Sanim / Wineman-Fisher, Vered / Al-Hamdani, Yasmine / Tkatchenko, Alexandre / Varma, Sameer

Journal of molecular biology

2020 Volume 433, Issue 3, Page(s) 166745

Abstract: Lysine methylation is a key regulator of protein-protein binding. The amine group of lysine can accept up to three methyl groups, and experiments show that protein-protein binding free energies are sensitive to the extent of methylation. These ... ...

Abstract	Lysine methylation is a key regulator of protein-protein binding. The amine group of lysine can accept up to three methyl groups, and experiments show that protein-protein binding free energies are sensitive to the extent of methylation. These sensitivities have been rationalized in terms of chemical and structural features present in the binding pockets of methyllysine binding domains. However, understanding their specific roles requires an energetic analysis. Here we propose a theoretical framework to combine quantum and molecular mechanics methods, and compute the effect of methylation on protein-protein binding free energies. The advantages of this approach are that it derives contributions from all local non-trivial effects of methylation on induction, polarizability and dispersion directly from self-consistent electron densities, and at the same time determines contributions from well-characterized hydration effects using a computationally efficient classical mean field method. Limitations of the approach are discussed, and we note that predicted free energies of fourteen out of the sixteen cases agree with experiment. Critical assessment of these cases leads to the following overarching principles that drive methylation-state recognition by protein domains. Methylation typically reduces the pairwise interaction between proteins. This biases binding toward lower methylated states. Simultaneously, however, methylation also makes it easier to partially dehydrate proteins and place them in protein-protein complexes. This latter effect biases binding in favor of higher methylated states. The overall effect of methylation on protein-protein binding depends ultimately on the balance between these two effects, which is observed to be tuned via several combinations of local features.
MeSH term(s)	Binding Sites ; Carrier Proteins/chemistry ; Carrier Proteins/metabolism ; Hydrogen Bonding ; Lysine/chemistry ; Lysine/metabolism ; Methylation ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Binding ; Proteins/chemistry ; Proteins/metabolism ; Solvents ; Structure-Activity Relationship
Chemical Substances	Carrier Proteins ; Proteins ; Solvents ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2020-12-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2020.166745
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 867: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Unique Inversion Events of Residues around the Backbone in the Turn Domain of β-Arches in Amylin Fibrils.

Atsmon-Raz, Yoav / Wineman-Fisher, Vered / Baram, Michal / Miller, Yifat

ACS chemical neuroscience

2018 Volume 10, Issue 3, Page(s) 1209–1213

Abstract: Orientational inversion events of residues along the turn domains of amylin fibrils have been detected. This exceptional phenomenon has been observed in isolated amylin fibrils and in the cross-seeding amylin-Aβ and amylin-NAC fibrils. These new findings ...

Abstract	Orientational inversion events of residues along the turn domains of amylin fibrils have been detected. This exceptional phenomenon has been observed in isolated amylin fibrils and in the cross-seeding amylin-Aβ and amylin-NAC fibrils. These new findings provide new avenues for detection of side chain flipping and side chain inversion events in turn domains and loops of various proteins.
MeSH term(s)	Amyloid/chemistry ; Amyloid/metabolism ; Humans ; Molecular Dynamics Simulation ; Protein Conformation
Chemical Substances	Amyloid
Language	English
Publishing date	2018-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.8b00554
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Methyl-Induced Polarization Destabilizes the Noncovalent Interactions of N-Methylated Lysines.

Rahman, Sanim / Wineman-Fisher, Vered / Nagy, Péter R / Al-Hamdani, Yasmine / Tkatchenko, Alexandre / Varma, Sameer

Chemistry (Weinheim an der Bergstrasse, Germany)

2021 Volume 27, Issue 42, Page(s) 11005–11014

Abstract: Lysine methylation can modify noncovalent interactions by altering lysine's hydrophobicity as well as its electronic structure. Although the ramifications of the former are documented, the effects of the latter remain largely unknown. Understanding the ... ...

Abstract	Lysine methylation can modify noncovalent interactions by altering lysine's hydrophobicity as well as its electronic structure. Although the ramifications of the former are documented, the effects of the latter remain largely unknown. Understanding the electronic structure is important for determining how biological methylation modulates protein-protein binding, and the impact of artificial methylation experiments in which methylated lysines are used as spectroscopic probes and protein crystallization facilitators. The benchmarked first-principles calculations undertaken here reveal that methyl-induced polarization weakens the electrostatic attraction of amines with protein functional groups - salt bridges, hydrogen bonds and cation-π interactions weaken by as much as 10.3, 7.9 and 3.5 kT, respectively. Multipole analysis shows that weakened electrostatics is due to the altered inductive effects, which overcome increased attraction from methyl-enhanced polarizability and dispersion. Due to their fundamental nature, these effects are expected to be present in many cases. A survey of methylated lysines in protein structures reveals several cases in which methyl-induced polarization is the primary driver of altered noncovalent interactions; in these cases, destabilizations are found to be in the 0.6-4.7 kT range. The clearest case of where methyl-induced polarization plays a dominant role in regulating biological function is that of the PHD1-PHD2 domain, which recognizes lysine-methylated states on histones. These results broaden our understanding of how methylation modulates noncovalent interactions.
MeSH term(s)	Hydrogen Bonding ; Lysine/metabolism ; Protein Binding ; Proteins/metabolism ; Static Electricity
Chemical Substances	Proteins ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2021-06-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202100644
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito