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MOLS sampling and its applications in structural biophysics

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Abstract

This review describes the MOLS method and its applications. This computational method has been developed in our laboratory primarily to explore the conformational space of small peptides and identify features of interest, particularly the minima, i.e., the low energy conformations. A systematic “brute-force” search through the vast conformational space for such features faces the insurmountable problem of combinatorial explosion, whilst other techniques, e.g., Monte Carlo searches, are somewhat limited in their region of exploration and may be considered inexhaustive. The MOLS method, on the other hand, uses a sampling technique commonly employed in experimental design theory to identify a small sample of the conformational space that nevertheless retains information about the entire space. The information is extracted using a technique that is a variant of the self-consistent mean field technique, which has been used to identify, for example, the optimal set of side-chain conformations in a protein. Applications of the MOLS method to understand peptide structure, predict the structures of loops in proteins, predict three-dimensional structures of small proteins, and arrive at the best conformation, orientation, and positions of a small molecule ligand in a protein receptor site have all yielded satisfactory results.

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Acknowledgment

We thank the Department of Science and Technology, Government of India and UGC, Government of India under Centre of Advanced Study program, for financial support.

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  1. Vadivel Kanagasabai

    Present address: Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

Authors and Affiliations

  1. Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, 600025, India

    L. Ramya, Shankaran Nehru Viji & Namasivayam Gautham

  2. Institute of Structural and Molecular Biology and Crystallography, Department of Biological Sciences, Birkbeck College, University of London, London, UK

    Pandurangan Arun Prasad

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Ramya, L., Nehru Viji, S., Arun Prasad, P. et al. MOLS sampling and its applications in structural biophysics. Biophys Rev 2, 169–179 (2010). https://doi.org/10.1007/s12551-010-0039-y

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