An application of experimental design using mutually orthogonal Latin squares in conformational studies of peptides

The theoretical prediction of the association of a flexible ligand with a protein receptor requires efficient sampling of the conformational space of the ligand. Several docking methodologies are currently available. We propose a new docking technique that performs well at low computational cost. The method uses mutually orthogonal Latin squares to efficiently sample the docking space. A variant of the mean field technique is used to analyze this sample to arrive at the optimum. The method has been previously applied to explore the conformational space of peptides and identify structures with low values for the potential energy. Here we extend this method to simultaneously identify both the low energy conformation as well as a 'high-scoring' docking mode. Application of the method to 56 protein-peptide complexes, in which the length of the peptide ligand ranges from three to seven residues, and comparisons with Autodock 3.05, showed that the method works well.

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“…The MOLS method has been presented in detail elsewhere [4,6,7]. For completeness the description is repeated in the supplementary material.…”

Section: The Mols Methodsmentioning

confidence: 99%

A new peptide docking strategy using a mean field technique with mutually orthogonal Latin square sampling

Prasad

Gautham

2008

J Comput Aided Mol Des

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“…MOLSDOCK [6,7,23] is a 'rigid receptor/flexible ligand' docking method developed using the MOLS method. The MOLS method has been presented in detail elsewhere [8,[24][25][26].…”

Section: Methodsmentioning

confidence: 99%

“…Each choice can lead to either the same, or to a different low energy structure. Previous experience [6][7][8]26,29] has shown us that generating about 1,500 structures is sufficient to cover the entire conformational space of a peptide or any other small molecule. The conformations so generated are clustered together to identify the few lowest energy structures that are possible for the peptide.…”

Section: Methodsmentioning

confidence: 99%

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

Paul

Gautham

2017

Journal of Molecular Graphics and Modelling

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“…They identified the lowest energy configurations of Met‐enkephalin to have a classic γ‐turn centered at residue Gly3 and a β‐turn at residues Gly 3 ‐Phe 4 . In earlier reports from our laboratory,16–19 we explored the conformational space of both Met‐ and Leu‐enkephalin using a technique we had developed called the mutually orthogonal Latin squares (MOLS) technique. An ensemble of conformations for both Met‐ and Leu‐enkephalin was generated using ECEPP3 force field in vacuum.…”

Section: Introductionmentioning

confidence: 99%

“…Earlier reports from our laboratory16–19, 30 had shown that MOLS sampling is extensive, and that the method identifies all experimental and computationally observed minimum energy structures of Met‐ and Leu‐enkephalin, besides locating other well‐folded structures of possible biological relevance. In this article, we compare the sampling behavior of the MD and MC simulations with that of the MOLS technique.…”

Section: Introductionmentioning

confidence: 99%

Conformational space exploration of met‐ and Leu‐enkephalin using the mols method, molecular dynamics, and Monte Carlo simulation—a comparative study

Ramya

Gautham

2011

Biopolymers

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We report here a comparative study of the molecular conformational energy landscape generated using the mutually orthogonal Latin squares (MOLS) method, molecular dynamics (MD), and Monte Carlo (MC) simulation. The MOLS method, as described earlier from our laboratory, uses an experimental design technique to rapidly and exhaustively sample the low energy conformations of a molecule. MD and MC simulations have been used to perform similar tasks. In the comparison reported here, the three methods were applied to a pair of neuropeptides, namely Met- and Leu-enkephalin. A set of 1500 conformations of these enkephalins were generated using these methods with CHARMM22 force field, and the resulting samples were analyzed to determine the extent and nature of coverage of the conformational space. The results indicate that the MOLS method samples a larger number of possible conformations and identifies conformations closer to the experimental structures than the MD and MC simulations.

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An application of experimental design using mutually orthogonal Latin squares in conformational studies of peptides

Cited by 10 publications

References 12 publications

A new peptide docking strategy using a mean field technique with mutually orthogonal Latin square sampling

A new peptide docking strategy using a mean field technique with mutually orthogonal Latin square sampling

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

Conformational space exploration of met‐ and Leu‐enkephalin using the mols method, molecular dynamics, and Monte Carlo simulation—a comparative study

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