Flexible Refinement of Protein-Ligand Docking on Manifolds.
Our work is motivated by energy minimization of biological macromolecules, an essential step in computational docking. By allowing some ligand flexibility, we generalize a recently introduced novel representation of rigid body minimization as an optimization on the [Formula: see text] manifold, rather than on the commonly used Special Euclidean groupSE(3). We show that the resulting flexible docking can also be formulated as an optimization on a Lie group that is the direct product of simpler Lie groups for which geodesics and exponential maps can be easily obtained. Our computational results for a local optimization algorithm developed based on this formulation show that it is about an order of magnitude faster than the state-of-the-art local minimization algorithms for computational protein-small molecule docking.
Division of Systems Eng., Boston University, hanieh@bu.edu.
Hanieh
H
Mirzaei
Dept, of Chemistry, Boston University, eavillar@bu.edu.
Elizabeth
E
Villar
Dept, of Bioinformatics, Boston University, semottar@bu.edu.
Scott
S
Mottarella
D. Kozakov, D. Beglov, and S. Vajda are with the Dept. of Biomedical Eng., Boston University, midas, dbeglov, vajda@bu.edu.
Dmitri
D
Beglov
Dept. of Electrical & Computer Eng., and Division of Systems Eng., Boston University, 8 Mary's St., Boston, MA 02215, yannisp@bu.edu.
Ioannis Ch
IC
Paschalidis
D. Kozakov, D. Beglov, and S. Vajda are with the Dept. of Biomedical Eng., Boston University, midas, dbeglov, vajda@bu.edu.
Sandor
S
Vajda
D. Kozakov, D. Beglov, and S. Vajda are with the Dept. of Biomedical Eng., Boston University, midas, dbeglov, vajda@bu.edu.
Dima
D
Kozakov
Division of Systems Eng., Boston University, hanieh@bu.edu.
Pirooz
P
Vakili