PrimeX - Protein structure prediction Software

PrimeX uses the OPLS-AA force field along with state-of-the-art technologies to refine protein crystal structures for computational drug discovery

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The prevailing geometric restraints employed in protein crystallography apply experimental bond length and angle terms as well as other restraint terms that have been subsequently added. However, some potential issues arise when refined structures are used in downstream computational modeling.

Two key characteristics of protein crystal structures that could affect the accuracy of subsequent structure-based modeling are:

• High-energy contacts interfere with computational chemistry calculations, and are often removed by the application of restrained energy minimization to the crystal structure; the danger with this procedure is the introduction of changes in the structure not supported by the X-ray data.
• Most protein crystal structures at typical resolutions do not include hydrogens in the model, which must be added after the end of refinement for many molecular mechanics calculations.

Traditionally, attempts to remediate the aforementioned issues are done after refinement, which shifts the control of structural results away from the scientists who are most familiar with the interpretation of diffraction experiments. PrimeX directly addresses these concerns by restraining protein geometry to OPLS-AA (one of the most accurate and widely-deployed force fields for studying protein/ligand systems) during X-ray refinement, and by adding hydrogens during refinement and fully accounting for their existence in all energy computations.

Furthermore, just as the inclusion of hydrogen atoms provides important information for structure validation of refinement results, PrimeX also features improved accounting of non-bonded interactions during refinement, which are central to understanding ligand binding. Thus, PrimeX provides a complete environment that facilitates refinement and produces accurate structures suitable for further computational modeling.

Software Link: PrimeX - Protein structure prediction Software

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Protein Preparation Wizard - Protein structure prediction Software

An easy-to-use tool for correcting common structural problems and creating reliable, all-atom protein models. Protein Preparation Wizard is a robust solution for ensuring a reasonable starting point at the outset of structure-based drug design projects, making it an attractive tool of choice for any chemist whose work relies upon accurate protein models.

Details

Successful structure-based modeling projects demand not only accurate software, but accurate starting structures as well. Left untreated, common problems with experimentally-derived structures can lead to wasted time and resources. Schrodinger's Protein Preparation Wizard is designed to help researchers ensure structural correctness at the outset of a project, equipping them with a high-confidence structure ideal for use with a wide variety of modeling applications.

Experienced modelers know that accurate starting structures are a prerequisite for successful computational drug design. Unfortunately, even when working with a high-resolution x-ray crystallographic structure, researchers can spend considerable time and effort correcting common problems such as missing hydrogen atoms, incomplete side chains and loops, ambiguous protonation states, and flipped residues.

The Protein Preparation Wizard aggregates, automates, and integrates the most frequently used tools and techniques in structure preparation, without shoehorning the researcher into a single inflexible process. Throughout the preparation workflow, a user can choose whether or not to apply any given operation, and because intermediate structures are all organized in the project table, it becomes trivial to share any result with a colleague or use outside applications when a specialized approach may be called for.

More than just a handful of utilities for minor structural corrections, the Protein Preparation Wizard is a robust solution for ensuring a reasonable starting point at the outset of structure-based drug design projects, making it an attractive tool of choice for any chemist whose work relies upon accurate protein models.

Software Link : Protein Preparation Wizard - Protein structure prediction Software

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Prime - Protein structure prediction Software

Prime is a fully-integrated protein structure prediction program. It provides an easy-to-use interface that takes a novice user intuitively from sequence to alignment to refined structure. Prime also provides expert users complete control over calculational settings to maximize accuracy of predictions. Prime is a powerful and complete tool for generating accurate receptor models for structure-based drug design.
Details
Rational drug design has proven to be an effective and cost-saving approach to drug development. Lead discovery using virtual screening and lead optimization through detailed understanding of ligand-receptor interactions are now indispensable components of pharmaceutical research. An accurate model of the receptor, particularly of the active site, is central to all structure-based drug design efforts. While the recent explosion in genomic data has elucidated many protein sequences, there remain many pharmaceutically relevant targets for which no accurate 3D model exist.

An accurate protein structure prediction can not only provide a model where an experimental structure is unavailable, but can also refine experimental structures obtained through X-ray crystallography or NMR, providing an even more accurate and detailed starting point for subsequent simulations and computational analyses.

Software Link : Prime - Protein structure prediction Software

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