Implementing efficient concerted rotations using Mathematica and C code

In this article we demonstrate a general and efficient metaprogramming implementation of concerted rotations using Mathematica. Concerted rotations allow the movement of a fixed portion of a polymer backbone with fixed bending angles, like a protein, while maintaining the correct geometry of the backbone and the initial and final points of the portion fixed. Our implementation uses Mathematica to generate a C code which is then wrapped in a library by a Python script. The user can modify the Mathematica notebook to generate a set of concerted rotations suited for a particular backbone geometry, without having to write the C code himself. The resulting code is highly optimized, performing on the order of thousands of operations per second

BOCS: Bottom-up Open-source Coarse-graining Software

We present the BOCS toolkit as a suite of open source software tools for parametrizing bottom-up coarse-grained (CG) models to accurately reproduce structural and thermodynamic properties of high-resolution models. The BOCS toolkit complements available software packages by providing robust implementations of both the multiscale coarse-graining (MS-CG) force-matching method and also the generalized-Yvon–Born–Green (g-YBG) method. The g-YBG method allows one to analyze and to calculate MS-CG potentials in terms of structural correlations. Additionally, the BOCS toolkit implements an extended ensemble framework for optimizing the transferability of bottom-up potentials, as well as a self-consistent pressure-matching method for accurately modeling the pressure equation of state for homogeneous systems. We illustrate these capabilities by parametrizing transferable potentials for CG models that accurately model the structure, pressure, and compressibility of liquid alkane systems and by quantifying the role of many-body correlations in determining the calculated pair potential for a one-site CG model of liquid methanol

MD Simulations of the dsRBP DGCR8 Reveal Correlated Motions that May Aid pri-miRNA Binding

Over the past decade, microRNAs (miRNAs) have been shown to affect gene regulation by basepairing with messenger RNA, and their misregulation has been directly linked with cancer. DGCR8, a protein that contains two dsRNA-binding domains (dsRBDs) in tandem, is vital for nuclear maturation of primary miRNAs (pri-miRNAs) in connection with the RNase III enzyme Drosha. The crystal structure of the DGCR8 Core (493–720) shows a unique, well-ordered structure of the linker region between the two dsRBDs that differs from the flexible linker connecting the two dsRBDs in the antiviral response protein, PKR. To better understand the interfacial interactions between the two dsRBDs, we ran extensive MD simulations of isolated dsRBDs (505–583 and 614–691) and the Core. The simulations reveal correlated reorientations of the two domains relative to one another, with the well-ordered linker and C-terminus serving as a pivot. The results demonstrate that motions at the domain interface dynamically impact the conformation of the RNA-binding surface and may provide an adaptive separation distance that is necessary to allow interactions with a variety of different pri-miRNAs with heterogeneous structures. These results thus provide an entry point for further in vitro studies of the potentially unique RNA-binding mode of DGCR8