Theory for trivial trajectory parallelization of multicanonical molecular dynamics and application to a polypeptide in water

Trivial trajectory parallelization of multicanonical molecular dynamics (TTP‐McMD) explores the conformational space of a biological system with multiple short runs of McMD starting from various initial structures. This method simply connects (i.e., trivially parallelizes) the short trajectories and generates a long trajectory. First, we theoretically prove that the simple trajectory connection satisfies a detailed balance automatically. Thus, the resultant long trajectory is regarded as a single multicanonical trajectory. Second, we applied TTP‐McMD to an alanine decapeptide with an all‐atom model in explicit water to compute a free‐energy landscape. The theory imposes two requirements on the multiple trajectories. We have demonstrated that TTP‐McMD naturally satisfies the requirements. The TTP‐McMD produces the free‐energy landscape considerably faster than a single‐run McMD does. We quantitatively showed that the accuracy of the computed landscape increases with increasing the number of multiple runs. Generally, the free‐energy landscape of a large biological system is unknown a priori. The current method is suitable for conformational sampling of such a large system to reduce the waiting time to obtain a canonical ensemble statistically reliable. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011