SimBioSys Inc.

eHiTS

Overview

eHiTS (electronic High Throughput Screening) is a molecular docking software application. It provides useful input for structure-based drug discovery and drug design by predicting binding modes of small molecules to protein receptors, and offers a powerful tool for virtual high throughput screening. eHiTS approaches the docking problem by employing unique algorithms for pose generation and scoring and by utilizing a large body of publicly available experimental data.

The Algorithm

eHiTS uses a systematic docking algorithm, that takes a divide and conquer approach to the docking problem. First, the ligand is divided into rigid fragments and flexible connecting chains. The rigid fragments are each docked INDEPENDENTLY in the receptor site, and then a fast graph matching algorithm finds compatible sets of poses of the fragments that can be reconnected to form the input ligand. A pre-defined number of poses are kept, reconnected with the appropriate flexible connecting chains and further optimized (using a local energy minimization algorithm) to give the final ligand pose. These poses are then scored to give the final ranking.

The Scoring Function

eHiTS employs a knowledge-based scoring function that includes physical terms as well as cheminformatics terms. The scoring function models interactions in protein-ligand complexes using interaction surface points (ISPs). ISPs of 23 types are placed on the surfaces of the ligand and the binding pocket and are used to model interactions between the ligand and the receptor, as well as ligand intramolecular interactions. Additional phenomenological terms, such as a burial factor, as well as several empirical terms complement the ISPs terms to form the eHiTS score.

Why Choose eHiTS?

Several features make eHiTS stand out in the crowded landscape of molecular docking applications. These have made the program one of the fastest and most accurate in the field, as has been shown by many independent studies. Here are some of the

  • Unbiased - since fragment are docked independently, eHiTS is unbiased toward specific poses and interactions.
  • Protonation state handling - eHiTS evaluates protonation states on the fly, thus relieving users from the hassle of preparing the system, and removing biases presented by pre-defined states.
  • Protein-family knowledge-base - using advanced cheminformatics techniques, protein families are characterized in terms of binding patterns, pharmacophores and active ligand profiles. This knowledge can be used in docking and scoring to improve accuracy and enrichments in virtual HTS.
[eHiTS Links]
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