A parameterization has been performed of the biologically important sterols cholesterol, ergosterol, and lanosterol for the CHARMM27 all-atom molecular mechanics force field. An automated parameterization method was used that involves fitting the potential to vibrational frequencies and eigenvectors derived from quantum-chemical calculations. The partial charges were derived by fitting point ch...

Energy minimization e orts to predict polypeptide structures assume their native conformation corre sponds to the global minimum free energy state Given this assumption the problem becomes that of develop ing e cient global optimization techniques applicable to polypeptide energy models This general structure prediction objective is also known as the protein fold ing problem Our prediction algo...

According to previous quantum mechanics/molecular mechanics (QM/MM) studies, camphor hydroxylation in cytochrome P450 is catalysed by a single water molecule which lowers the computed B3LYP/CHARMM barrier by about 4 kcal mol(-1). Gas-phase B3LYP model studies for a variety of different substrates show the generality of this effect. Its origin is an electrostatic enhancement of hydrogen bonding ...

The conversion of 4-chlorobenzoyl-CoA to 4-hydroxybenzoyl-CoA catalyzed by 4-chlorobenzoyl-CoA dehalogenase is investigated using combined QM/MM approaches. The calculated potential of mean force at the PM3/CHARMM level supports the proposed nucleophilic aromatic substitution mechanism. In particular, a Meisenheimer intermediate was found, stabilized by hydrogen bonds between the benzoyl carbon...

The development of an integrated software environment for protein structure refinement is reported. Energy minimization is combined with geometric embedding in the refinement program. The energy minimization procedure is used to sample the conformational space and find a group of low energy structures for further improvement. The distance geometry also known as geometric embedding is then appli...

Searching conformational ensembles of proteins remains a challenge in atomistic simulation of biomolecules. One approach to accelerate the protein sampling is to take advantage of rough energy surface from the coarse-grained model and, at the same time, to persist atomistic details from the all-atom model. Multiscale enhanced sampling (MSES) of all atoms and topology-based coarse-grained replic...

Recently, the synthesis of a molecule has been reported that belongs to a Lysine based, branched cyclic peptide class. This work explores the ability of such molecules to preserve the 3D geometry of the Trypsin's Active Site (TAS) by applying an integrated framework of automated computer procedures. The following four factors a) D/L chirality, b) different amino acids at different positions of ...

Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure-based computer-aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently ...

A previous article proposed an electronic structure-based polarizable potential, called the explicit polarization (X-POL) potential, to treat many-body polarization and charge delocalization effects in polypeptides. Here, we present a variational version of the X-POL potential, in which the wave function of the entire molecular system is variationally optimized to yield the minimum total electr...