Convex-PL: a novel knowledge-based potential for protein-ligand interactions deduced from structural databases using convex optimization

Maria Kadukova 1, 2 Sergei Grudinin 1
1 NANO-D - Algorithms for Modeling and Simulation of Nanosystems
Inria Grenoble - Rhône-Alpes, LJK - Laboratoire Jean Kuntzmann, INPG - Institut National Polytechnique de Grenoble
Abstract : We present a novel optimization approach to train a free-shape distance-dependent protein-ligand scoring function called Convex-PL. We do not impose any functional form of the scoring function. Instead, we decompose it into a polynomial basis and deduce the expansion coefficients from the structural knowledge base using a convex formulation of the optimization problem. Also, for the training set we do not generate false poses with molecular docking packages, but use constant RMSD rigid-body deformations of the ligands inside the binding pockets. This allows the obtained scoring function to be generally applicable to scoring of structural ensembles generated with different docking methods. We assess the Convex-PL scoring function using data from D3R Grand Challenge 2 submissions and the docking test of the CASF 2013 study. We demonstrate that our results outperform the other 20 methods previously assessed in CASF 2013. The method is available at http://team.inria.fr/nano-d/ software/Convex-PL/.
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https://hal.inria.fr/hal-01591154
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Submitted on : Wednesday, September 20, 2017 - 9:57:51 PM
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Maria Kadukova, Sergei Grudinin. Convex-PL: a novel knowledge-based potential for protein-ligand interactions deduced from structural databases using convex optimization. Journal of Computer-Aided Molecular Design, Springer Verlag, 2017, 31 (10), pp.943-958. ⟨10.1007/s10822-017-0068-8⟩. ⟨hal-01591154⟩

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