Molecular Docking for Ligand-Receptor Binding Process Based on Heterogeneous Computing

Molecular docking aims to predict possible drug candidates for many diseases, and it is computationally intensive. Particularly, in simulating the ligand-receptor binding process, the binding pocket of the receptor is divided into subcubes, and when the ligand is docked into all cubes, there are many molecular docking tasks, which are extremely time-consuming. In this study, we propose a heterogeneous parallel scheme of molecular docking for the binding process of ligand to receptor to accelerate simulating. The parallel scheme includes two layers of parallelism, a coarse-grained layer of parallelism implemented in the message-passing interface (MPI) and a fine-grained layer of parallelism focused on the graphics processing unit (GPU). At the coarse-grain layer of parallelism, a docking task inside one lattice is assigned to one unique MPI process, and a grouped master-slave mode is used to allocate and schedule the tasks. Meanwhile, at the fine-gained layer of parallelism, GPU accelerators undertake the computationally intensive computing of scoring functions and related conformation spatial transformations in a single docking task. The results of the experiments for the ligand-receptor binding process show that on a multicore server with GPUs the parallel program has achieved a speedup ratio as high as 45 times in flexible docking and as high as 54.5 times in semiflexible docking, and on a distributed memory system, the docking time for flexible docking and that for semiflexible docking gradually decrease as the number of nodes used in the parallel program gradually increases. The scalability of the parallel program is also verified in multiple nodes on a distributed memory system and is approximately linear.

EXPRESS: Remembered Together: Social interaction facilitates retrieval while reducing individuation of features within bound representations.

When encountering social scenes, there appears to be rapid and automatic detection of social interactions. Representations of interacting people appear to be bound together via a mechanism of joint attention, which results in enhanced memory, even when participants are unaware that memory is required. However, even though access is facilitated for socially bound representations, we predicted that the individual features of these representations are less efficiently encoded, and features can therefore migrate between the constituent interacting individuals. This was confirmed in Experiment 1, where overall memory for interacting compared to non-interacting dyads was facilitated but binding of features within an individual was weak, resulting in feature migration errors. Experiment 2 demonstrated the role of conscious strategic processing, where participants were aware that memory would be tested. With such awareness, attention can be focused on individual objects allowing the binding of features. The results support an account of two forms of processing: An initial automatic social binding process where interacting individuals are represented as one episode in memory facilitating access; and a further stage where attention can be focused on each individual enabling the binding of features within individual objects.

Probing the Suitability of Different Ca2+ Parameters for Long Simulations of Diisopropyl Fluorophosphatase

Organophosphate hydrolases are promising as potential biotherapeutic agents to treat poisoning with pesticides or nerve gases. However, these enzymes often need to be further engineered in order to become useful in practice. One example of such enhancement is the alteration of enantioselectivity of diisopropyl fluorophosphatase (DFPase). Molecular modeling techniques offer a unique opportunity to address this task rationally by providing a physical description of the substrate-binding process. However, DFPase is a metalloenzyme, and correct modeling of metal cations is a challenging task generally coming with a tradeoff between simulation speed and accuracy. Here, we probe several molecular mechanical parameter combinations for their ability to empower long simulations needed to achieve a quantitative description of substrate binding. We demonstrate that a combination of the Amber19sb force field with the recently developed 12-6 Ca2+ models allows us to both correctly model DFPase and obtain new insights into the DFP binding process.

Insights into the Binding and Covalent Inhibition Mechanism of PF-07321332 to SARS-CoV-2 Mpro

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been causing the COVID-19 pandemic resulting in several million death were reported. Numerous investigations have been carried out to discover a compound that can inhibit the biological activity of SARS-CoV-2 main protease, which is an enzyme related to the viral replication. Among these, PF-07321332 is currently under clinical trial for COVID-19 therapy. Therefore, in this work, atomistic and electronic simulations were performed to unravel the binding and covalent inhibition mechanism of the compound to Mpro. Initially, 5 µs of steered-molecular dynamics simulations were carried out to evaluate the ligand-binding process to SARS-CoV-2 Mpro. Successfully generated bound state between two molecules showed the important role of the PF-07321332 pyrrolidinyl group and the residues Glu166 and Gln189 in the ligand-binding process. Moreover, from the MD-refined structure, quantum mechanics/molecular mechanics (QM/MM) calculations were carried out to unravel the reaction mechanism for the formation of thioimidate product from SARS-CoV-2 Mpro and PF07321332 inhibitor. We found that the catalytic triad Cys145–His41–Asp187 of SARS-CoV-2 Mpro plays important role in the activation of PF-07321332 covalent inhibitor, which renders the deprotonation of Cys145 and, thus, facilitates further reaction. Our results are definitely beneficial for better understanding on the inhibition mechanism and designing new effective inhibitors for SARS-CoV-2 Mpro.

REVIEW OF THE STRENGTH OF FOX GLUE IN DEVELOPMENT BOOK VOLS TECHNOLOGY USING THE YOSHINO 602 ENGINE

Competition in the manufacture of raw materials for printing and binding purposes is undeniable, as is the hot glue required for binding on books. The method used in this writing is descriptive method, namely by presenting factual information obtained from observations obtained and seen in the Industrial Practices place. The binding technique without thread or perfect binding is used for binding books, magazines and others. The main ingredient in the perfect binding binding process is glue. Glue greatly affects the production result, if the adjustments are not done properly the temperature of the glue and the thickness of the glue. The purpose of writing this paper is to determine the adhesion strength of Fox brand glue and to find out the problems that occur in the gluing unit during the volume of the book "Technology Development in the Yoshino 602 machine. Fox glue has high adhesion strength and the adhesion dries quickly so as not to waste a lot of time. , Fox glue is also very suitable for binding paper types (coated and uncoated) with a temperature of 1650C-1800C and a side glue temperature of 1400C on the Yoshino 602 machine. So Fox brand glue is very suitable for the binding process of "Technology Development" books using a machine. Yoshino 602 at PT. Putra Nugraha Sentosa. The problems that occur in the gluing unit are the temperature of the glue, the thickness of the glue on the roller and the glue roller, due to the lack of accuracy of the machine operator.Keywords: Adhesion, Glue and Machine