Kosmos: A Computational Web Server for Biomolecular Dynamics

Since 2012, KOREA SKKU MORPH SERVER (KOSMOS, http://bioengineering.skku.ac.kr/kosmos/) has successfully provided computational biology society with an online platform to analyze biomolecular dynamics automatically. The detailed work flow is as follows: i) representation of a biological structure, including DNA/RNA and protein, as an elastic network model (ENM) in which physical and chemical interactions among atoms are modeled as linear springs, ii) harmonic or anharmonic analysis to reveal its featuring dynamics such as normal modes and transition pathway, respectively, iii) deposition of simulation results into the database for visualization and future bioinformatics study.

In harmonic analysis, ENM based normal mode analysis (NMA) is performed to compute both vibration frequencies and their corresponding mode shapes, which are strongly related with functional movements of biomolecules. This useful information can be employed either as a finger print to identify biomolecular dynamics in atomic detail or as a general clue to link between structure and function in macromolecules. So far, KOSMOS has completed NMA for more than 130,000 biomolecular structures (>94% of the total number of structures currently available in Protein Data Bank).

Anharmonic analysis is slightly different from harmonic analysis. It focuses more on how to generate feasible transition pathway between two known conformations of an identical biomolecule. KOSMOS offers the elastic network interpolation (ENI) method in which a given conformation morphs into the target conformation by optimizing a potential energy based cost function. It yields a structurally and energetically favorable transition pathway.

Although ENI is able to give an insight on biofunctional motion at a relatively inexpensive cost, a long-time and large-scale simulation is still challenging task. To overcome this limitation, a bond-boost method is suggested to accelerate the speed of conventional molecular dynamics simulation by elevating the level of potential energy. KOSMOS will equip this interesting feature in the near future.