Assessing AMBER force fields for protein folding in an implicit solvent

2018 ◽  
Vol 20 (10) ◽  
pp. 7206-7216 ◽  
Author(s):  
Qiang Shao ◽  
Weiliang Zhu
Keyword(s):  
Protein Folding ◽  
Force Fields ◽  
Md Simulations ◽  
Implicit Solvent ◽  
Amber Force Fields ◽  
Folding Thermodynamics

MD simulations quantitatively assess the availability and limitation of six recently developed AMBER force fields in reproducing protein native structures and measuring folding thermodynamics under implicit solvent conditions.

Thermodynamics of Helix formation in small peptides of varying lengthin vacuo, implicit solvent and explicit solvent: Comparison between AMBER force fields

2019 ◽  
Vol 18 (03) ◽  
pp. 1950015
Author(s):  
Zhaoxi Sun ◽  
Xiaohui Wang
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Hydrogen Bonds ◽  
Force Fields ◽  
Implicit Solvent ◽  
Conformational Ensemble ◽  
Helix Formation ◽  
Solvent Models ◽  
Explicit Solvent ◽  
Amber Force Fields

Helix formation is of great significance in protein folding. The helix-forming tendencies of amino acids are accumulated along the sequence to determine the helix-forming tendency of peptides. Computer simulation can be used to model this process in atomic details and give structural insights. In the current work, we employ equilibrate-state free energy simulation to systematically study the folding/unfolding thermodynamics of a series of mutated peptides. Two AMBER force fields including AMBER99SB and AMBER14SB are compared. The new 14SB force field uses refitted torsion parameters compared with 99SB and they share the same atomic charge scheme. We find that in vacuo the helix formation is mutation dependent, which reflects the different helix propensities of different amino acids. In general, there are helix formers, helix indifferent groups and helix breakers. The helical structure becomes more favored when the length of the sequence becomes longer, which arises from the formation of additional backbone hydrogen bonds in the lengthened sequence. Therefore, the helix indifferent groups and helix breakers will become helix formers in long sequences. Also, protonation-dependent helix formation is observed for ionizable groups. In 14SB, the helical structures are more stable than in 99SB and differences can be observed in their grouping schemes, especially in the helix indifferent group. In solvents, all mutations are helix indifferent due to protein–solvent interactions. The decrease in the number of backbone hydrogen bonds is the same with the increase in the number of protein–water hydrogen bonds. The 14SB in explicit solvent is able to capture the free energy minima in the helical state while 14SB in implicit solvent, 99SB in explicit solvent and 99SB in implicit solvent cannot. The helix propensities calculated under 14SB agree with the corresponding experimental values, while the 99SB results obviously deviate from the references. Hence, implicit solvent models are unable to correctly describe the thermodynamics even for the simple helix formation in isolated peptides. Well-developed force fields and explicit solvents are needed to correctly describe the protein dynamics. Aside from the free energy, differences in conformational ensemble under different force fields in different solvent models are observed. The numbers of hydrogen bonds formed under different force fields agree and they are mostly determined by the solvent model.

scholarly journals Continuous B- to A- Transition in Protein-DNA Binding - How Well Is It Described by Current AMBER Force Fields?

2022 ◽  
Author(s):  
Petr Jurecka ◽  
Marie Zgarbova ◽  
Filip Cerny ◽  
Jan Salomon
Keyword(s):  
Force Fields ◽  
Md Simulations ◽  
Binding Motif ◽  
Dna Complexes ◽  
Continuous Transition ◽  
Correct Sequence ◽  
Protein Dna Interactions ◽  
Intermediate States ◽  
Amber Force Fields ◽  
Dna Complex

When DNA interacts with a protein, its structure often undergoes significant conformational adaptation. Perhaps the most common is the transition from canonical B-DNA towards the A-DNA form, which is not a two-state, but rather a continuous transition. The A- and B- forms differ mainly in sugar pucker P (north/south) and glycosidic torsion χ (high-anti/anti). The combination of A-like P and B-like χ (and vice versa) represents the nature of the intermediate states lying between the pure A- and B- forms. In this work, we study how the A/B equilibrium and in particular the A/B intermediate states, which are known to be over-represented at protein-DNA interfaces, are modeled by current AMBER force fields. Eight protein-DNA complexes and their naked (unbound) DNAs were simulated with OL15 and bsc1 force fields as well as an experimental combination OL15χOL3. We found that while the geometries of the A-like intermediate states in the molecular dynamics (MD) simulations agree well with the native X-ray geometries found in the protein-DNA complexes, their populations (stabilities) are significantly underestimated. Different force fields predict different propensities for A-like states growing in the order OL15 < bsc1 < OL15χOL3, but the overall populations of the A-like form are too low in all of them. Interestingly, the force fields seem to predict the correct sequence-dependent A-form propensity, as they predict larger populations of the A-like form in naked (unbound) DNA in those steps that acquire A-like conformations in protein-DNA complexes. The instability of A-like geometries in current force fields may significantly alter the geometry of the simulated protein-DNA complex, destabilize the binding motif, and reduce the binding energy, suggesting that refinement is needed to improve description of protein-DNA interactions in AMBER force fields.

CONFORMATIONAL DYNAMICS OF HIV-1 PROTEASE: A COMPARATIVE MOLECULAR DYNAMICS SIMULATION STUDY WITH MULTIPLE AMBER FORCE FIELDS

2012 ◽  
Vol 10 (06) ◽  
pp. 1250018 ◽  
Author(s):  
BISWA RANJAN MEHER ◽  
MATTAPARTHI VENKATA SATISH KUMAR ◽  
SMRITI SHARMA ◽  
PRADIPTA BANDYOPADHYAY
Keyword(s):  
Force Field ◽  
Active Site ◽  
Force Fields ◽  
Conformational Dynamics ◽  
Md Simulations ◽  
Order Parameters ◽  
Dynamics Simulation ◽  
Active Site Cavity ◽  
Amber Force Fields ◽  
Hiv 1

Flap dynamics of HIV-1 protease (HIV-pr) controls the entry of inhibitors and substrates to the active site. Dynamical models from previous simulations are not all consistent with each other and not all are supported by the NMR results. In the present work, the effect of force field on the dynamics of HIV-pr is investigated by MD simulations using three AMBER force fields ff99, ff99SB, and ff03. The generalized order parameters for amide backbone are calculated from the three force fields and compared with the NMR S2 values. We found that the ff99SB and ff03 force field calculated order parameters agree reasonably well with the NMR S2 values, whereas ff99 calculated values deviate most from the NMR order parameters. Stereochemical geometry of protein models from each force field also agrees well with the remarks from NMR S2 values. However, between ff99SB and ff03, there are several differences, most notably in the loop regions. It is found that these loops are, in general, more flexible in the ff03 force field. This results in a larger active site cavity in the simulation with the ff03 force field. The effect of this difference in computer-aided drug design against flexible receptors is discussed.

Assessment of AMBER Force Fields for Simulations of ssDNA

2021 ◽  
Vol 17 (2) ◽  
pp. 1208-1217
Author(s):  
Thomas J. Oweida ◽  
Ho Shin Kim ◽  
Johnny M. Donald ◽  
Abhishek Singh ◽  
Yaroslava G. Yingling
Keyword(s):  
Force Fields ◽  
Amber Force Fields

scholarly journals High-resolution mining of the SARS-CoV-2 main protease conformational space: supercomputer-driven unsupervised adaptive sampling

2021 ◽  
Author(s):  
Théo Jaffrelot Inizan ◽  
Frédéric Célerse ◽  
Olivier Adjoua ◽  
Dina El Ahdab ◽  
Luc-Henri Jolly ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
High Resolution ◽  
Adaptive Sampling ◽  
Force Fields ◽  
Sampling Strategy ◽  
Md Simulations ◽  
Conformational Space ◽  
Many Body ◽  
Polarizable Force Fields ◽  
Main Protease

We provide an unsupervised adaptive sampling strategy capable of producing μs-timescale molecular dynamics (MD) simulations of large biosystems using many-body polarizable force fields (PFFs).

VERIFICATION OF THE GENERALIZED BORN MODEL AT SHORT DISTANCES

2013 ◽  
Vol 13 (06) ◽  
pp. 1340020
Author(s):  
XIAOCHUAN TANG ◽  
YONG DUAN
Keyword(s):  
Analytical Solutions ◽  
Md Simulations ◽  
Solvation Energy ◽  
Implicit Solvent ◽  
Generalized Born ◽  
Simple Description ◽  
Born Model ◽  
Solvent Models ◽  
Potential Methods ◽  
Gb Model

The generalized Born (GB) model, one of the implicit solvent models, is widely applied in molecular dynamics (MD) simulations as a simple description of the solvation effect. In the GB model, an empirical function called the Still's formula, with the algorithmic simplicity, is utilized to calculate the solvation energy due to the polarization, termed as ΔG pol . Applications of the GB model have exhibited reasonable accuracy and high computational efficiency. However, there is still room for improvements. Most of the attempts to improve the GB model focus on optimizing effective Born radii. Contrarily, limited researches have been performed to improve the feasibility of the Still's formula. In this paper, analytical methods was applied to investigate the validity of the Still's formula at short distance. Taking advantage of the toroidal coordinates and Mehler–Fock transform, the analytical solutions of the GB model at short distances was derived explicitly for the first time. Additionally, the solvation energy was numerically computed using proper algorithms based on the analytical solutions and compared with ΔG pol calculated in the GB model. With the analysis on the deficiencies of the Still's formula at short distances, potential methods to improve the validity of the GB model were discussed.

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