A generalized-ensemble technique, multicanonical sampling, is used to study the folding of a 34-residue human parathyroid hormone fragment. An all-atom model of the peptide is employed and the protein-solvent interactions are approximated by an implicit solvent. Our results demonstrate that generalized-ensemble simulations are well suited to sample low-energy structures of such large polypeptid...

This paper reviews state-of-the-art methods and presents new perspectives of implicit modeling, together with their relations with Constructive-SolidGeometry, for the computation and analysis of molecular surfaces. The link between implicit modeling techniques and the generation of molecular surfaces is possible thanks to the representation of the molecule as the iso-surface of an implicit func...

Binding affinity prediction with implicit solvent models remains a challenge in virtual screening for drug discovery. In order to assess the predictive power of implicit solvent models in docking techniques with Amber scoring, three generalized Born models (GBHCT, GBOBCI, and GBOBCII) available in Dock 6.7 were utilized, for determining the binding affinity of a large set of β-cyclodextrin comp...

pH is a ubiquitous regulator of biological activity, including protein-folding, protein-protein interactions, and enzymatic activity. Existing constant pH molecular dynamics (CPHMD) models that were developed to address questions related to the pH-dependent properties of proteins are largely based on implicit solvent models. However, implicit solvent models are known to underestimate the desolv...

One of the most challenging problems in protein structure prediction is improvement of homology models (structures within 1-3 A C(alpha) rmsd of the native structure), also known as the protein structure refinement problem. It has been shown that improvement could be achieved using in vacuo energy minimization with molecular mechanics and statistically derived continuously differentiable hybrid...

To investigate whether implicit solvent models are appropriate for mechanistic studies of conformational transition in proteins, a recently developed generalized Born model (GBSW) was applied to a small signaling protein, chemotaxis protein Y (CheY), with different combinations of the phosphorylation state and conformation of the system; the results were compared to explicit solvent simulations...

Molecular mechanics with generalised Born and surface area solvation (MM/GBSA) is a popular method to calculate the free energy of the binding of ligands to proteins. It involves molecular dynamics (MD) simulations with an explicit solvent of the protein-ligand complex to give a set of snapshots for which energies are calculated with an implicit solvent. This change in the solvation method (exp...

The heterogeneous dielectric generalized Born (HDGB) methodology is an the extension of the GBMV model for the simulation of integral membrane proteins with an implicit membrane environment. Three large integral membrane proteins, the bacteriorhodopsin monomer and trimer and the BtuCD protein, were simulated with the HDGB model in order to evaluate how well thermodynamic and dynamic properties ...