Functional characterization of a protein sequence is one of the most frequent problems in biology. This task is usually facilitated by an accurate three-dimensional (3-D) structure of the studied protein. In the absence of an experimentally determined structure, comparative or homology modeling often provides a useful 3-D model for a protein that is related to at least one known protein structu...

Taking into account dynamical behavior and/or structural inaccuracies of receptor-ligand systems becomes increasingly important in structure-based drug design. Here, we describe the development of consensus Adaptation of Fields for Molecular Comparison (AFMoC) (abbreviated as AFMoCcon) models that account for multiple ligand conformations in an ensemble of protein configurations. Ligand and rec...

Protein sequence alignment is at the core of a variety of fundamental tasks such as homology modeling, fold recognition, evolutionary studies and more. Much attention was dedicated over recent years for alignment of sequences in the twilight zone, where pairwise sequence alignment methods (e.g. BLAST) perform poorly. State of the art methods employ sequence profiles, and sometimes meta-sequence...

SUMMARY PERMOL is a new restraint-based program for homology modeling of proteins. Restraints are generated from the information contained in structures of homologous template proteins. Employing the restraints generated by PERMOL, three-dimensional structures are obtained using MD programs such as DYANA or CNS. In contrast to other programs PERMOL is mainly based on the use of dihedral angle i...

The success of ligand docking calculations typically depends on the quality of the receptor structure. Given improvements in protein structure prediction approaches, approximate protein models now can be routinely obtained for the majority of gene products in a given proteome. Structure-based virtual screening of large combinatorial libraries of lead candidates against theoretically modeled rec...

Quantification of statistical significance is essential for the interpretation of protein structural similarity. To address this, a random model for protein structure comparison was developed. Novelty of the model is threefold. First, a sample of random structure comparisons is restricted to molecules of the same size and shape as the superposition of interest. Second, careful selection of the ...

Abbreviations 1D D one-dimensional; 1D structure D one-dimensional (e.g., sequence or string of secondary structure); 2D D two-dimensional; 2D structure D two-dimensional (e.g., interresidue distances); 3D D three-dimensional; 3D structure D three-dimensional (coordinates of protein structure); PDB D Protein Data Bank of experimentally determined 3D structures of proteins; SWISS-PROT D database...

Modeling by homology is the most accurate computational method for translating an amino acid sequence into a protein structure. Homology modeling can be divided into two sub-problems, placing the polypeptide backbone and adding side-chains. We present a method for rapidly predicting the conformations of protein side-chains, starting from main-chain coordinates alone. The method involves using f...