Dynamics-based alignment of proteins
Sequence and structure alignment algorithms are long-standing techniques to study proteins. However, protein structures are dynamic rather than static, and understanding the relation between protein function and dynamics is fundamental for comprehending the protein structure–dynamics–function relationship. In recent years, we have developed several tools for comparison of protein dynamics that are sequence and structure independent, contributing to the development of the field of comparative dynamics. These algorithms perform alignment of ANM modes of motions and are based on the commonly used Needleman-Wunsch and Smith-Waterman algorithms for global and local sequence alignment.
Using the above-mentioned algorithms, we can detect global and local dynamics conservation between proteins. In addition, we showed that we can cluster proteins based on dynamical similarity.
Energy-like scores are widely used to score putative protein-protein and protein-small molecule docked complexes. Other scores are used in threading and in sequence to structure fold recognition. Some of these scores utilize atomic-level potentials, others employ residue-level potentials or a combination of both. Many of these potentials are knowledge based, others are force field based, or a combination of force-field-based and knowledge-based potentials. In many cases, the total energy can be expressed or approximated as a linear combination of a parameter set. Then, these parameters can be optimized using Linear Programming algorithms such as Simplex or Interior-Point. Using this approach, we develop protein folding and protein-protein docking potentials.
Small molecule docking
Small-molecule docking is a computational technique that aims to identify the correct pose of which a small molecule binds to its target site within a given protein structure. Molecular docking has become an increasingly important tool for drug discovery. When the three-dimensional structure of the target protein is known and the desired site within it is identified, large libraries of small molecules can be scanned using docking algorithms to identify potentials binders. We employ various docking algorithms to identify correct binding pose of known inhibitors and perform large-scale virtual screening to identify new drugs.