ProtoMcol: A Molecular Dynamics Research Framework for Algorithmic Development

OxyR is a transcriptional factor, which activates transcription of antioxidant genes. In this study, we constructed a structural model for the full-length OxyR from Shewanella oneidensis MR-1 using threading and comparative modeling techniques. To further study the conformational changes, we also performed molecular dynamics simulations on the activation domain of OxyR. Molecular dynamics simulations were performed using GROMACS force field under periodic boundary conditions. The particle mesh Ewald (PME) method was used to treat long-range electrostatic interactions. The simulation results show that the oxidized form is very stable while the reduced form is quite flexible. Our results suggest that the reduced form provides structural flexibility for disulfide bond formation and which in turn regulates its function.

The iData Toolkit is a toolkit that allows programmers to create interactive, type-safe, dynamic web applications with state on a high level of abstraction. The key element of this toolkit is the iData element. An iData element is a form that is generated automatically from a type definition and that can be plugged in in the web page of a web application. In this paper we show how this automatic generation of forms has been implemented. The technique relies essentially on generic programming. It has resulted in a concise and flexible implementation. The kernel of the implementation can be reused for any graphical package. The iData Toolkit is an excellent demonstration of the expressive power of modern generic (poly-typical) programming techniques.

In recent years, short peptide self-assembled materials, prepared under the control of the thermolysin catalyst, have been investigated extensively and shown to acquire various morphologies and fun...

Application Generator (AG) can help save time of software development. Some AG has its own DSL (Domain Specific Language) to direct the generated application outcome. In this research, we developed a DSL using the syntax notation text with simple structure that can assist AG in the process of generating source code for desktop-based database application using Java. DSL development is applying the methodology of DSL development from Czarnecki. The development for AG involves three areas of knowledge, i.e. domain engineering, DSL, and AG (compiler). Domain engineering is required to understand the target application domain to be generated, i.e. MySQL database and Java programming language with Swing UI. The DSL is developed in five phases, i.e. decision-making, analysis, design, implementation, and development. The AG itself is developed in Java platform. The DSL and AG developed in this research has shown that the DSL can help programmer to develop Java desktop-based database applications by utilizing DSL to map MySQL database into Java Swing UI, and employ AG to generate applications directly from DSL source. It is expected that further development of this research is to support more flexible application development.

We present the current status of development of our code for performing Molecular Dynamics (MD) simulations exploiting a polarizable force field based on the Fluctuating Charge (FQ) method and non-Periodic Boundary Conditions (NPBC). Continuing on the path set in a previous work, we increased the capabilities of the code by implementing a number of new features, including: a non-iterative algorithm for rigid trigonal molecule simulations; two additional temperature coupling schemes; a meta-dynamics based approach for effective free energy evaluations. Although these are well known algorithms, each present in one or more widely used MD packages, they have now been tested, for the first time, in the context of the FQ model coupled with NPBC. As case studies, we considered three aqueous ions of increasing charge, namely Na+, Ca2+ and La3+, at infinite dilution. In particular, by exploiting a computational approach recently proposed by our group and based on the metadynamics technique, we focused on the important role played by solvent polarization on ionic hydration structures, also investigating the free energy landscapes of ion coordination and the water exchange rates. Such an approach, previously tested with standard non-polarizable models, was applied here to evaluate the effects of explicit polarization on water exchange barriers between different solvent coordination structures. Moreover, we have analyzed and discussed in some detail non-linear electrostatic effects arising from solvent polarization while going from a mono- to a di- and trivalent ion.

In this note, we address some issues concerning the accurate pressure calculation of Coulomb systems with periodic boundary conditions. First, we prove that the formulas for the excess part of the pressure with Ewald summation also reduce to the ensemble average of one-third of the ratio between the potential energy and the volume so that the comments on our previous work in a recent paper by Onegin et al (2024 J. Phys. A: Math. Theor. 57 205002) are incorrect. Second, we demonstrate that in charge non-neutral systems, the pressure expression must be corrected to include interactions with the neutralizing background. This addresses the issues about pressure computation in LAMMPS raised in the paper by Onegin et al. Numerical experiments are performed to verify that the pressure obtained via Ewald summation with corrected terms agrees with the average pressure using thermodynamics for the non-neutral OCP system, and are independent of the splitting parameter in the Ewald summation.

Metal ions play significant roles in biological systems. Accurate molecular dynamics (MD) simulations on these systems require a validated set of parameters. Although there are more detailed ways to model metal ions, the nonbonded model, which employs a 12-6 Lennard-Jones (LJ) term plus an electrostatic potential is still widely used in MD simulations today due to its simple form. However, LJ parameters have limited transferability due to different combining rules, various water models and diverse simulation methods. Recently, simulations employing a Particle Mesh Ewald (PME) treatment for long-range electrostatics have become more and more popular owing to their speed and accuracy. In the present work we have systematically designed LJ parameters for 24 +2 metal (M(II)) cations to reproduce different experimental properties appropriate for the Lorentz-Berthelot combining rules and PME simulations. We began by testing the transferability of currently available M(II) ion LJ parameters. The results showed that there are differences between simulations employing Ewald summation with other simulation methods and that it was necessary to design new parameters specific for PME based simulations. Employing the thermodynamic integration (TI) method and performing periodic boundary MD simulations employing PME, allowed for the systematic investigation of the LJ parameter space. Hydration free energies (HFEs), the ion-oxygen distance in the first solvation shell (IOD) and coordination numbers (CNs) were obtained for various combinations of the parameters of the LJ potential for four widely used water models (TIP3P, SPC/E, TIP4P and TIP4PEW). Results showed that the three simulated properties were highly correlated. Meanwhile, M(II) ions with the same parameters in different water models produce remarkably different HFEs but similar structural properties. It is difficult to reproduce various experimental values simultaneously because the nonbonded model underestimates the interaction between the metal ions and water molecules at short range. Moreover, the extent of underestimation increases successively for the TIP3P, SPC/E, TIP4PEW and TIP4P water models. Nonetheless, we fitted a curve to describe the relationship between ε (the well depth) and radius (Rmin/2) from experimental data on noble gases to facilitate the generation of the best possible compromise models. Hence, by targeting different experimental values, we developed three sets of parameters for M(II) cations for three different water models (TIP3P, SPC/E and TIP4PEW). These parameters we feel represent the best possible compromise that can be achieved using the nonbonded model for the ions in combination with simple water models. From a computational uncertainty analysis we estimate that the uncertainty in our computed HFEs is on the order of ±1kcal/mol. Further improvements will require more advanced non-bonded models likely with inclusion of polarization.

The simulation of charged and/or strongly polar solutes represents a challenge for standard molecular-dynamics techniques. The use of periodic boundary conditions (PBCs) leads to artifacts due to the interaction between two replicas in the presence of the long-range Coulomb forces. A way to avoid these problems is the use of nonperiodic boundary conditions. A possible realization is to consider a finite system, a sphere, embedded in a reaction field described by the method of the images. In the present work the modified image approximation has been implemented in a molecular-dynamics code and optimized for the use of two standard solvents, water and acetonitrile. The methodology has then been applied to investigate the conformational changes in water-solvated alanine dipeptide. The free-energy surface calculated with this method is comparable to that obtained with PBC.

Grid Inhomogeneous Solvation Theory (GIST) maps out solvation thermodynamic properties on a fine meshed grid and provides a statistical mechanical formalism for thermodynamic end-state calculations. However, differences in how long-range nonbonded interactions are calculated in molecular dynamics engines and in the current implementation of GIST have prevented precise comparisons between free energies estimated using GIST and those from other free energy methods such as thermodynamic integration (TI). Here, we address this by presenting PME-GIST, a formalism by which particle mesh Ewald (PME)-based electrostatic energies and long-range Lennard-Jones (LJ) energies are decomposed and assigned to individual atoms and the corresponding voxels they occupy in a manner consistent with the GIST approach. PME-GIST yields potential energy calculations that are precisely consistent with modern simulation engines and performs these calculations at a dramatically faster speed than prior implementations. Here, we apply PME-GIST end-state analyses to 32 small molecules whose solvation free energies are close to evenly distributed from 2 kcal/mol to -17 kcal/mol and obtain solvation energies consistent with TI calculations (R2 = 0.99, mean unsigned difference 0.8 kcal/mol). We also estimate the entropy contribution from the second and higher order entropy terms that are truncated in GIST by the differences between entropies calculated in TI and GIST. With a simple correction for the high order entropy terms, PME-GIST obtains solvation free energies that are highly consistent with TI calculations (R2 = 0.99, mean unsigned difference = 0.4 kcal/mol) and experimental results (R2 = 0.88, mean unsigned difference = 1.4 kcal/mol). The precision of PME-GIST also enables us to show that the solvation free energy of small hydrophobic and hydrophilic molecules can be largely understood based on perturbations of the solvent in a region extending a few solvation shells from the solute. We have integrated PME-GIST into the open-source molecular dynamics analysis software CPPTRAJ.

Technologically, lithium tantalate is one of the most important ferroelectric materials with a low poling field that has several applications in the field of photonics and memory switching devices. Due to strong localization coupled with discreteness in a nonlinear K-G lattice, there is a formation of breathers and multi-breathers that manifest in the localized peaks across the domains in polarization-space-time plot. To probe the quantum states related to discrete breathers for the application in nano technology, the same K-G lattice is quantized to give rise to quantum breathers (QBs) that are explained by a periodic boundary condition. Secondly, in a non-periodic boundary condition, the temporal evolution of quanta shows interesting behavior as a function of impurity that is important from design viewpoint for the THz applications.

We report on the application of SPIN for model-checking C source code which is generated out of a textual domain-specific language (DSL). We have built a tool which automatically generates the necessary SPIN wrapper code using (meta-)information available at the DSL level. The approach is part of a larger tool-chain for developing mission critical applications. The main purpose of SPIN is for bug-finding where error traces resulting from SPIN can be automatically replayed at the DSL level and yield concise explanations in terms of a temporal specification DSL. The tool-chain is applied in some large scale industrial applications.

One of the important modules of a black-box automatic program grader is a "checker". In programming competition environment, a checker is a program written for the purpose to check the output of the contestant's program for a task that has many solutions. Usually, a checker is written manually as needed. In this paper, the idea of the output checker in the programming competition environment is extended to input checker and source code checker as a part of the automatic grader in our programming learning environment. Input checker validates the input coverage. The source code checker is used to validate a set of properties from a source code against the given coding specification. A Domain-Specific Language (DSL) grammar is designed and developed as a specification for the automatic generation of the output, input, and source code checkers. The DSL grammar and the checker generator tool set are used to evaluate source codes in our programming class. By writing the checkers specification in DSL, the specification is automatically documented and can be reused for similar properties.

Domain specific languages (DSLs) offer the potential for using a small, specialized and highly expressive programming language to concisely represent solutions for a particular domain of problems. The DSL approach is in stark contrast to that of a general programming language that attempts to provide a means to represent solutions for a broad range of problems. DSLs may incorporate constructs and syntactical features that not only relate to the problem context, but also to the execution platform. DSLs thus provide a potential for reducing development time and thereby cutting business costs. At present this approach is likely more appropriate to prototyping and rapid experimental work; but as technologies to implement DSLs improve they may become more beneficial and cost effective for developing marketable products. In this paper we present a DSL, called OptiSDR, aimed to improve developer productivity for development of software defined radio (SDR) applications deployed on heterogeneous computing architectures (HCAs). OptiSDR is designed for HCAs that adhere to certain combinations of processing devices, namely FPGAs, graphics processing units, and multi-core general purpose processors. Our aim to improve developer productivity in multiple ways was achieved, with development cycles for parallel DSP routines for SDR reduced to few hours as opposed to days for CUDA-C development cycles. OptiSDR uses automatic code generation for structured parallel SDR patterns, and performs automatic profiling to generate faster execution kernels with speed-ups of more than 50× compared to other sequential implementations while reducing manual effort in porting and tuning code. Therefore this paper reports on a study confirming the potential to speed up when using OptiSDR for prototyping SDR applications.

The binding of biotin to avidin is one of the strongest in nature with absolute free energy of binding, ΔA(0) = -20.4 kcal/mol. Therefore, this complex became a target for a large number of computational studies, which all, however, are based on approximate techniques or simplified models and have led to a wide range of results Therefore, ΔA(0) is calculated here by rigorous statistical mechanical methods and models that consider long-range electrostatics. (1) We apply our method, "hypothetical scanning molecular dynamics with thermodynamic integration" (HSMD-TI) to avidin-biotin modeled by periodic boundary conditions with particle mesh ewald (PME). (2) We apply the double decoupling method (DDM) to this system modeled by the spherical solvent boundary potential (SSBP) and the generalized solvent boundary potential (GSBP). The corresponding results for neutral biotin, ΔA(0) = -29.1 ± 0.8 and -25.2 ± 0.5 kcal/mol are significantly lower than the experimental value; we also provide the result for a charged biotin, ΔA(0) = -33.3 ± 0.8 kcal/mol. It is plausible to suggest that this disagreement with the experiment may stem from ignoring the (positive) contribution of a mobile loop that changes its structure upon ligand binding.

A decision support system (DSS) for the integration of hydrologic process modeling and risk evaluation of the surface water management alternatives in a river basin is developed. The DSS, named CTIWM, is aimed at supporting the testing and evaluation of water management policies and at facilitating integration of user-selected scenarios into planning strategies of the water resource system in the Chikugo River basin, a multipurpose multireservoir system. CTIWM uses a module library that contains compatible modules for simulating a variety of hydrologic processes. Different numerical models are invoked through a user interface menu, which facilitates communications between users and models in a friendly way. The source code was developed by using object-oriented programming techniques. The result shows that the use of DSSs may effectively improve the speed and quality of water management and give users more flexibility in analyzing different scenarios.