PROTDES: CHARMM toolbox for computational protein design

We present an open-source software able to automatically mutate any residue positions and find the best aminoacids in an arbitrary protein structure without requiring pairwise approximations. Our software, PROTDES, is based on CHARMM and it searches automatically for mutations optimizing a protein folding free energy. PROTDES allows the integration of molecular dynamics within the protein design. We have implemented an heuristic optimization algorithm that iteratively searches the best aminoacids and their conformations for an arbitrary set of positions within a structure. Our software allows CHARMM users to perform protein design calculations and to create their own procedures for protein design using their own energy functions. We show this by implementing three different energy functions based on different solvent treatments: surface area accessibility, generalized Born using molecular volume and an effective energy function. PROTDES, a tutorial, parameter sets, configuration tools and examples are freely available at http://soft.synth-bio.org/protdes.html

Automated Builder and Database of Protein/Membrane Complexes for Molecular Dynamics Simulations

Molecular dynamics simulations of membrane proteins have provided deeper insights into their functions and interactions with surrounding environments at the atomic level. However, compared to solvation of globular proteins, building a realistic protein/membrane complex is still challenging and requires considerable experience with simulation software. Membrane Builder in the CHARMM-GUI website (http://www.charmm-gui.org) helps users to build such a complex system using a web browser with a graphical user interface. Through a generalized and automated building process including system size determination as well as generation of lipid bilayer, pore water, bulk water, and ions, a realistic membrane system with virtually any kinds and shapes of membrane proteins can be generated in 5 minutes to 2 hours depending on the system size. Default values that were elaborated and tested extensively are given in each step to provide reasonable options and starting points for both non-expert and expert users. The efficacy of Membrane Builder is illustrated by its applications to 12 transmembrane and 3 interfacial membrane proteins, whose fully equilibrated systems with three different types of lipid molecules (DMPC, DPPC, and POPC) and two types of system shapes (rectangular and hexagonal) are freely available on the CHARMM-GUI website. One of the most significant advantages of using the web environment is that, if a problem is found, users can go back and re-generate the whole system again before quitting the browser. Therefore, Membrane Builder provides the intuitive and easy way to build and simulate the biologically important membrane system

Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al

openmm/openmm: OpenMM 8.1.1

<p>This is a patch release containing the following changes.</p> <p>#4351: Fixed bug in large blocks optimization with triclinic boxes #4364: Fixed error in barostat</p&gt

openmm/openmm: OpenMM 8.1.0 beta

<p>This release contains many performance improvements, particularly to the CUDA and OpenCL platforms. The largest speedups are for very large systems, in the range of 1 million particles or more, which can now be much faster. Other simulations will also often be faster, though by smaller amounts. Some examples of cases that have been specifically optimized include PME on the OpenCL platform; very small systems (less than 3000 particles) on the CUDA platform; CUDA or OpenCL simulations on Windows; CUDA simulations that are parallelized across multiple GPUs; and CUDA or OpenCL simulations that use CustomHbondForce.</p> <p>This release adds a new class called ATMForce that implements the Alchemical Transfer Method. This is an efficient, relatively easy to use method for doing alchemical free energy calculations. See <a href="https://doi.org/10.1021/acs.jcim.1c01129">https://doi.org/10.1021/acs.jcim.1c01129</a> for more information.</p> <p>There is a new XTCReporter class for writing simulation trajectories to XTC files. This is an alternative to DCD for efficiently storing trajectories. It stores coordinates with reduced precision, which leads to significantly smaller files.</p> <p>When running local energy minimizations, it is now possible to pass a reporter to the minimizer. This allows you to monitor the progress of minimization and optionally to stop it early when custom criteria are met.</p> <p>The GromacsTopFile class now supports GROMACS files that use GROMOS force fields.</p> <p>This release adds a new piece of low level infrastructure for use when writing plugins: the CustomCPPForceImpl class. It is used for writing plugins that are implemented entirely in platform-independent C++. This is useful, for example, when writing plugins that interface to other libraries or programs. By using the new mechanism, the amount of code needed for plugins of that sort is dramatically reduced.</p> <p>One significant feature has been removed: GromacsTopFile can no longer read files that use implicit solvent. GROMACS removed all support for implicit solvent a few years ago, and it had not worked correctly for several years before that. OpenMM continued to support GROMACS files with implicit solvent, but it required you to have an increasingly obsolete version of GROMACS installed on your computer. That support has now been removed.</p&gt