Computer simulations have become a mature and useful method in studies of molecules of life. As a part of structural bioinformatics carefully planned numerical experiments provide unique data on dynamics and properties of biomolecules. In this article a review of the state of art of molecular dynamics (MD) studies is presented. Current trends involving the steered MD, milestoning and coarse grained MD are described and some examples of MD applications in bio- and nano-technology are presented. The progress in hardware, such as parallel computing and purpose-built processors, is also addressed.
Dihydrofolate reductase (DHFR, EC 1.5.1.3) is one of the enzymes active in the folate cycle which plays an important role in DNA synthesis. Inhibition of DHFR is a key element in the treatment of many diseases, including cancer and AIDS related infections. A search for new selective inhibitors is motivated by the resistance to common drugs observed in the course of treatment. In this paper, results of a detailed computer analysis of human DHFR interactions with the lipophilic inhibitor piritrexim (PTX) are presented. It was found that the NADPH cofactor contributes 30% of the total PTX-enzyme interaction energy. Substitution of the highly conserved Glu30 with alanine does not lead to the release of the inhibitor from the hDHFR pocket. The important L22F point mutation does affect PTX orientation but does not change the binding energy. Simulations of the dynamics of binary hDHFR-TX complexes were performed with the use of Extensible Systematic Force Field (ESFF) and the results indicate structural changes in the enzyme induced by NADPH binding.
Caddisfly (Trichopera) can glue diverse material underwater with a silk fiber. This makes it a particularly interesting subject for biomimetcs. Better understanding of silk composition and structure could lead to an adhesive capable to close bleeding wounds or to new biomaterials. However, while spiderweb or silkworm secretion is well researched, caddisfly silk is still poorly understood. Here we report a first nanomechanical analysis of H. Angustipennis caddisfly silk fiber. An Atomic Force Microscope (AFM) imaging shows dense 150 nm bumps on silk surface, which can be identified as one of features responsible for its outstanding adhesive properties. AFM force spectroscopy at the fiber surface showed, among others, characteristic saw like pattern. This pattern is attributed to sacrificial bond stretching and enhances energy dissipation in mechanical deformation. Similarities of some force curves observed on Tegenaria domestica spiderweb and caddisfly silk are also discussed. Steered Molecular Dynamics simulations revealed that the strength of short components of Fib-H HA species molecules, abundant in Trichoptera silk is critically dependent on calcium presence.
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