Accurate Evaluation of Ion Conductivity of the Gramicidin A Channel Using a Polarizable Force Field without Any Corrections.

Classical molecular dynamic (MD) simulation of membrane proteins faces significant challenges in accurately reproducing and predicting experimental observables such as ion conductance and permeability due to its incapability of precisely describing the electronic interactions in heterogeneous systems. In this work, the free energy profiles of K(+) and Na(+) permeating through the gramicidin A channel are characterized by using the AMOEBA polarizable force field with a total sampling time of 1 μs. Our results indicated that by explicitly introducing the multipole terms and polarization into the electrostatic potentials, the permeation free energy barrier of K(+) through the gA channel is considerably reduced compared to the overestimated results obtained from the fixed-charge model.

Structural basis for activity regulation of MLL family methyltransferases.

The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood.

The Effect of Codon Mismatch on the Protein Translation System.

Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult.

Hidden Conformation Events in DNA Base Extrusions: A Generalized Ensemble Path Optimization and Equilibrium Simulation Study.

DNA base extrusion is a crucial component of many biomolecular processes. Elucidating how bases are selectively extruded from the interiors of double-strand DNAs is pivotal to accurately understanding and efficiently sampling this general type of conformational transitions. In this work, the on-the-path random walk (OTPRW) method, which is the first generalized ensemble sampling scheme designed for finite-temperature-string path optimizations, was improved and applied to obtain the minimum free energy path (MFEP) and the free energy profile of a classical B-DNA major-groove base extrusion pathway.

Microfluidic multi-analyte gradient generator.

A microfluidic device was developed to produce temporal concentration gradients of multiple analytes. Four on-chip pumps delivered pulses of three analytes and buffer to a 14-cm channel where the pulses were mixed to homogeneity. The final concentration of each analyte was dependent on the temporal density of the pulses from each pump.