Empirical Scoring Functions for Advanced Protein−Ligand Docking with PLANTS

Abstract

In this paper we present two empirical scoring functions, PLANTS(CHEMPLP) and PLANTS(PLP), designed for our docking algorithm PLANTS (Protein-Ligand ANT System), which is based on ant colony optimization (ACO). They are related, regarding their functional form, to parts of already published scoring functions and force fields. The parametrization procedure described here was able to identify several parameter settings showing an excellent performance for the task of pose prediction on two test sets comprising 298 complexes in total. Up to 87% of the complexes of the Astex diverse set and 77% of the CCDC/Astex clean listnc (noncovalently bound complexes of the clean list) could be reproduced with root-mean-square deviations of less than 2 A with respect to the experimentally determined structures. A comparison with the state-of-the-art docking tool GOLD clearly shows that this is, especially for the druglike Astex diverse set, an improvement in pose prediction performance. Additionally, optimized parameter settings for the search algorithm were identified, which can be used to balance pose prediction reliability and search speed.

Construction and Optimization of Structure-Based Virtual Screening Protocols to Identify Cyclooxygenase-1 Inhibitors Using Open Babel, Spores and Plants

“…PLANTS1.2, which uses stochastic optimization algorithms called Ant Colony Optimization (ACO) [16] was employed to perform the docking simulations. Structure Protonation and Recognition System (SPORES) software (http://www.tcd.unikonstanz.de/research/spores.php), which assigns atom and bond type according to TRIPOS force field convention [18] was employed to virtually prepare the COX-1 structure as the protein target in the docking simulations using PLANTS.…”

“…The construction of SBVS protocol to identify COX-1 inhibitors using PLANTS docking software version 1.2 (PLANTS1.2) [16] is presented in this article. Iterative procedures were employed to optimize the protocol in order to obtain a protocol that can redock the reference ligand accurately compared to the pose of the reference crystal structure.…”

Molecular docking approach to identify potential anticancer compounds from Begonia (Begonia sp)

“…Open Babel version 2.2.3 (www.openbabel.org), employing Monte Carlo search with a force field of MMFF94 was used to virtually prepare the EFGR protein target and ligand, together with Structure Protonation and Recognition System (SPORES) software (www.tcd.unikonstanz.de/research/spores.php) [14][15]. Molecular docking simulation was subsequently performed by PLANTS1.2 [16].…”

The Identification of the 2-Phenylphthalazin-1(2H)-one Scaffold as a New Decorable Core Skeleton for the Design of Potent and Selective Human A3 Adenosine Receptor Antagonists

“…45 phenol (ZM-241385) was redocked into the crystal structure of the hA 2A AR (PDB code: 3EML) with different docking algorithms and scoring functions, as already described. 29,46 Then, rmsd values between predicted and crystallographic positions of ZM-241385 were calculated for each of the docking algorithms.…”