Exploring the conformational space of protein loops using a mean field technique with MOLS sampling

Abstract

We have recently developed a computational technique that uses mutually orthogonal Latin square sampling to explore the conformational space of oligopeptides in an exhaustive manner. In this article, we report its use to analyze the conformational spaces of 120 protein loop sequences in proteins, culled from the PDB, having the length ranging from 5 to 10 residues. The force field used did not have any information regarding the sequences or structures that flanked the loop. The results of the analyses show that the native structure of the loop, as found in the PDB falls at one of the low energy points in the conformational landscape of the sequences. Thus, a large portion of the structural determinants of the loop may be considered intrinsic to the sequence, regardless of either adjacent sequences or structures, or the interactions that the atoms of the loop make with other residues in the protein or in neighboring proteins.

iMOLSDOCK: Induced-fit docking using mutually orthogonal Latin squares (MOLS)

“…The potential energy for each conformation is calculated. The m 2 energy values are then analyzed using a variant of the mean field technique [10,27] to arrive at the conformation with the lowest energy. We note here that there are a very large number of ways in which we can choose the m 2 points [28].…”

Exploring conformational space using a mean field technique with MOLS sampling

“…An example is shown for the case of φ 11. e.g. for and Gautham 2003and Gautham , 2004a, to analyse protein loops (Kanagasabai et al 2007), to predict protein structure (Arunachalam et al 2006) and to explore peptide docking.…”

MOLS sampling and its applications in structural biophysics

“…This technique of using MOLS in a variant of the SCMFT has been applied to sample the conformational space of peptides Gautham 2003, 2004a;Ramya and Gautham 2009), to analyze protein loops (Kanagasabai et al 2007), to predict protein structure (Arunachalam et al 2006), and to explore the docking of peptides and other small molecules to receptor sites on proteins (Arun Prasad and Gautham 2008;Viji et al 2009). …”

“…There have also been several attempts to classify loop structures (Leszczynski and Rose 1986;Ring et al 1992;Efimov 1993). We used the MOLS algorithm to map the conformational space of loops (Kanagasabai et al 2007). The loops were chosen from 3,868 nonredundant high quality protein structures from the PDB database.…”

“…The above calculations were repeated by including in the energy function a statistical mean force potential (Kanagasabai et al 2007). Such a potential had earlier been constructed (Sippl 1995) by analysis of all known high-resolution protein structures.…”