Changes in the conformations of conjugated molecules affect the optical and electronic properties significantly. Hydrostatic pressure has been used to probe the conformations of biphenyl (C12H10) and deuterated biphenyl (C12D10) at liquid-helium temperatures. Infrared ~IR! spectra of these materials have been taken up to a pressure of 2 GPa. A disappearance of certain IR absorption peaks has be...

In recent years an effort has been made to supplement traditional methods for drug discovery by computerassisted “structure-based design.” The structure-based approach involves (among other issues) reasoning about the geometry of drug molecules (or ligands) and about the different spatial conformations that these molecules can attain. This is a preliminary report on a set of tools that we are d...

A number of measures have been used in the structural biology literature to compare the shapes or conformations of biological macromolecules. However, the issue of how to compare two ensembles of conformations has received far less attention. Herein, the problem of how to quantitatively compare two such ensembles is addressed in several different ways using concepts from probability and informa...

Many protein-protein interactions (PPIs) are compelling targets for drug discovery, and in a number of cases can be disrupted by small molecules. The main goal of this study is to examine the mechanism of binding site formation in the interface region of proteins that are PPI targets by comparing ligand-free and ligand-bound structures. To avoid any potential bias, we focus on ensembles of liga...

Cryogenic electron tomography (cryo-ET) allows structural determination of biomolecules in their native environment ( situ ). Its potential providing information on the dynamics macromolecular complexes cells is still largely unexploited, due to challenges data analysis. The crowded cell and continuous conformational changes make difficult disentangling heterogeneity. We present HEMNMA-3D, whic...

An analysis of the nature and distribution of disallowed Ramachandran conformations of amino acid residues observed in high resolution protein crystal structures has been carried out. A data set consisting of 110 high resolution, non-homologous, protein crystal structures from the Brookhaven Protein Data Bank was examined. The data set consisted of a total of 18,708 non-Gly residues, which were...

We present a verified computational model of the SH3 domain transition state (TS) ensemble. This model was built for three separate SH3 domains using experimental phi-values as structural constraints in all-atom protein folding simulations. While averaging over all conformations incorrectly considers non-TS conformations as transition states, quantifying structures as pre-TS, TS, and post-TS by...

We present a recently developed clustering method and specify it for the problem of identification of metastable conformations in non-equilibrium biomolecular time series. The approach is based on variational minimization of some novel regularized clustering functional. In context of conformational analysis, it allows to combine the features of standard geometrical clustering techniques (like t...