BROMOC Suite: Monte Carlo/Brownian Dynamics Suite for Studies of Ion Permeation and DNA transport in Biological and Artificial Pores with Effective Potentials Pablo M. De Biase,* Suren Markosyan, and Sergei Noskov* The transport of ions and solutes by biological pores is central for cellular processes and has a variety of applications in mod- ern biotechnology. The time scale involved in the polymer transport across a nanopore is beyond the accessibility of con- ventional MD simulations. Moreover, experimental studies lack sufficient resolution to provide details on the molecular under- pinning of the transport mechanisms. BROMOC, the code pre- sented herein, performs Brownian dynamics simulations, both serial and parallel, up to several milliseconds long. BROMOC can be used to model large biological systems. IMC-MACRO software allows for the development of effective potentials for solute–ion interactions based on radial distribution function from all-atom MD. BROMOC Suite also provides a versatile set of tools to do a wide variety of preprocessing and postsimula- tion analysis. We illustrate a potential application with ion and ssDNA transport in MspA nanopore. V C 2014 Wiley Periodicals, Inc. DOI: 10.1002/jcc.23799 Introduction BROMOC program is designed to produce a trajectory of mobile ions and a coarse-grained DNA in a nanopores or membrane proteins. [1] There is a serial and a parallel version both written in Fortran-90. The formal method of development was presented by Roux and Im labs. [2–4] The grand canonical Monte Carlo (GCMC) method is used to maintain the desired electrochemical conditions in the buffer regions of the simulation system; allow- ing for both symmetric and asymmetric buffers. The presence of the implicit membrane permits for the application of transmem- brane potentials. BROMOC can also be used to perform Brown- ian Dynamics (BD) and/or Monte Carlo moves (MCMs) of ions in presence of the potential given by the pore, membrane and bulk solution. BROMOC Suite includes numerous tools to per- form a variety of analyses as well as to set up parameters for BROMOC runs. BROMOC is used by setting up an input file with the corresponding keywords and commands to execute the desired simulation. We also provide an independent tool for the development of solute–ion and ion–ion effective potentials from all-atom MD site–site radial distribution functions (RDFs) so-called IMC-MACRO. [5] This option allows the user to parame- terize solvent-mediated interaction potentials that are then read by the program. In the following sections, we will explain each keyword and its corresponding function. As an illustration, we will present development of new effective potential parameters for NaCl in water, study of ion conductance in a model biological pore and finally simulation of ss-DNA translocation study across MspA, a bacterial beta-barrel protein pore with great promises in ssDNA sequencing. Methods The novel programs in BROMOC Suite are BROMOC, IMC- MACRO, and BROMOC Tools. The main BROMOC keywords and functions are explained subsequently jointly with IMC-MACRO and all programs within BROMOC Tools. For a detailed descrip- tion of each keyword, refer to the documentation within BRO- MOC Suite tarball which can be found at http://noskovlab. com. Tutorials for preparing BROMOC simulations as well as for computing effective potentials/excess chemical potential (ECP) can be found at the same location. BROMOC Suite is free software: it can be redistributed it and/or modified it under the terms of the GNU General Public License as pub- lished by the Free Software Foundation. The developed code is based on evaluation version of BRO- MOC software reported in Ref. [1] . The novel features include novel methods to manipulate DNA structure, application of steering forces, on-the-fly averaging of computed parameters, visualization options as well as integrated software for effec- tive potential development. The list of keywords and corre- sponding functions is provided below. BROMOC: Keywords and Functions System The system is delimited by the portion of space in which mobile particles are bound, including the buffer regions. With the key- word SYSTEM, system dimensions such as size, position, and shape of the system can be defined as well as other physical P. M. De Biase, S. Markosyan, S. Noskov Centre for Molecular Simulation, Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada, T2N 1N4 E-mail: pablo.debiase@ucalgary.ca; snoskov@ucalgary.ca Contract grant sponsor: NHGRI; Contract grant number: R01 HG005095; Contract grant sponsor: National Sciences and Engineering Research Council (NSERC); Contract grant number: Discovery Grant RGPIN-315019 to S.Y.N. V C 2014 Wiley Periodicals, Inc. 264 Journal of Computational Chemistry 2015, 36, 264–271 WWW.CHEMISTRYVIEWS.COM SOFTWARE NEWS AND UPDATES WWW.C-CHEM.ORG