A New Implicit Solvent Model for Brownian Dynamics Simulation: Solvent-Accessible Surface Area Dependent Effective Charge Model

2004 ◽  
Vol 3 (4) ◽  
pp. 129-136 ◽  
Author(s):  
Tadashi ANDO ◽  
Toshiyuki MEGURO ◽  
Ichiro YAMATO
Keyword(s):  
Brownian Dynamics ◽  
Accessible Surface Area ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Implicit Solvent ◽  
Brownian Dynamics Simulation ◽  
Charge Model ◽  
Solvent Model ◽  
Accessible Surface ◽  
Solvent Accessible Surface

scholarly journals PAMAM dendrimer: a pH-controlled nanosponge

2017 ◽  
Vol 95 (9) ◽  
pp. 991-998 ◽  
Author(s):  
Prabal K. Maiti
Keyword(s):  
Accessible Surface Area ◽  
Pamam Dendrimer ◽  
Low Ph ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Water Molecules ◽  
Accessible Volume ◽  
Accessible Surface ◽  
Solvent Accessible Surface ◽  
Ph Controlled

Using fully atomistic molecular dynamics simulation that are several hundred nanoseconds long, we demonstrate the pH-controlled sponge action of PAMAM dendrimer. We show how at varying pH levels, the PAMAM dendrimer acts as a wet sponge; at neutral or low pH levels, the dendrimer expands noticeably and the interior of the dendrimer opens up to host several hundreds to thousands of water molecules depending on the generation number. Increasing the pH (i.e., going from low pH to high pH) leads to the collapse of the dendrimer size, thereby expelling the inner water, which mimics the ‘sponge’ action. As the dendrimer size swells up at a neutral pH or low pH due to the electrostatic repulsion between the primary and tertiary amines that are protonated at this pH, there is dramatic increase in the available solvent accessible surface area (SASA), as well as solvent accessible volume (SAV).

scholarly journals Variational implicit-solvent predictions of the dry–wet transition pathways for ligand–receptor binding and unbinding kinetics

2019 ◽  
Vol 116 (30) ◽  
pp. 14989-14994 ◽  
Author(s):  
Shenggao Zhou ◽  
R. Gregor Weiß ◽  
Li-Tien Cheng ◽  
Joachim Dzubiella ◽  
J. Andrew McCammon ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Brownian Dynamics ◽  
Minimum Energy ◽  
Planck Equation ◽  
Environmental Water ◽  
Dynamics Simulation ◽  
Implicit Solvent ◽  
Brownian Dynamics Simulation ◽  
Stochastic Motion ◽  
Solvent Model

Ligand–receptor binding and unbinding are fundamental biomolecular processes and particularly essential to drug efficacy. Environmental water fluctuations, however, impact the corresponding thermodynamics and kinetics and thereby challenge theoretical descriptions. Here, we devise a holistic, implicit-solvent, multimethod approach to predict the (un)binding kinetics for a generic ligand–pocket model. We use the variational implicit-solvent model (VISM) to calculate the solute–solvent interfacial structures and the corresponding free energies, and combine the VISM with the string method to obtain the minimum energy paths and transition states between the various metastable (“dry” and “wet”) hydration states. The resulting dry–wet transition rates are then used in a spatially dependent multistate continuous-time Markov chain Brownian dynamics simulation and the related Fokker–Planck equation calculations of the ligand stochastic motion, providing the mean first-passage times for binding and unbinding. We find the hydration transitions to significantly slow down the binding process, in semiquantitative agreement with existing explicit-water simulations, but significantly accelerate the unbinding process. Moreover, our methods allow the characterization of nonequilibrium hydration states of pocket and ligand during the ligand movement, for which we find substantial memory and hysteresis effects for binding vs. unbinding. Our study thus provides a significant step forward toward efficient, physics-based interpretation and predictions of the complex kinetics in realistic ligand–receptor systems.

scholarly journals Screening of druggable conformers of α-synuclein using molecular dynamics simulation

2020 ◽  
Vol 10 (3) ◽  
pp. 5338-5347
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Secondary Structure ◽  
Surface Area ◽  
Accessible Surface Area ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Binding Pockets ◽  
Accessible Surface ◽  
Solvent Accessible Surface

Intrinsically disordered proteins (IDPs) are becoming an engaging prospect for therapeutic intervention by small drug-like molecules. IDPs structural binding pockets and their flexibility exist as a challenging target for standard druggable approaches. Hence, in this study, we have performed and identified the most probable druggable conformers from molecular dynamics simulation on α-synuclein based on the structural parameters: radius of gyration (Rg), solvent accessible surface area (SASA) and the standard secondary structure content. We found the conformers showing lower solvent accessible surface area and higher secondary structure content of α-helical are defined to be suitable binding pockets for druggability.

scholarly journals Mutations in RBD of SARS-CoV-2 Omicron variant result stronger binding to human ACE2 protein

2021 ◽  
Author(s):  
Cecylia Severin Lupala ◽  
Yongjin Ye ◽  
Hong Chen ◽  
Xiaodong Su ◽  
Haiguang Liu
Keyword(s):  
Complex Structure ◽  
Tight Binding ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Original Strain ◽  
Receptor Binding Domain ◽  
Bonding Interaction ◽  
Accessible Surface ◽  
Dynamics Simulations ◽  
Solvent Accessible Surface

The spreading of SARS-CoV-2 virus resulted the COVID-19 pandemic, which has caused more than 5 millions of death globally. Several major variants of SARS-CoV-2 have emerged and placed challenges in controlling the infections. The recently emerged Omicron variant raised serious concerns about reducing efficacy of antibodies or vaccines, due to its vast mutations. We modelled the complex structure of human ACE2 protein and the receptor binding domain of Omicron variant, then conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron variant RBD binds more strongly to the human ACE2 protein than the original strain. The mutation at the ACE2-RBD interface enhanced the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area.

scholarly journals Analysis of Two-State Folding Using Parabolic Approximation I: Hypothesis

2016 ◽  
Author(s):  
Robert S Sade
Keyword(s):  
Gibbs Energy ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Parabolic Approximation ◽  
Energy Functions ◽  
State Ensemble ◽  
The Mean ◽  
Accessible Surface ◽  
Transition State Ensemble ◽  
Solvent Accessible Surface

A model which treats the denatured and native conformers of spontaneously-folding fixed two-state systems as being confined to harmonic Gibbs energy-wells has been developed. Within the assumptions of this model the Gibbs energy functions of the denatured (DSE) and the native state (NSE) ensembles are described by parabolas, with the mean length of the reaction coordinate (RC) being given by the temperature-invariant denaturant m value. Consequently, the ensemble-averaged position of the transition state ensemble (TSE) along the RC, and the ensemble-averaged Gibbs energy of the TSE are determined by the intersection of the DSE and the NSE-parabolas. The equations derived enable equilibrium stability and the rate constants to be rationalized in terms of the mean and the variance of the Gaussian distribution of the solvent accessible surface area of the conformers in the DSE and the NSE. The implications of this model for protein folding are discussed.

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