Research Progress of Artificial Intelligence and Molecular Simulation in Drug Design / 医药导报

With the deepening of modern drug research,traditional computer simulation can not meet the needs of future drug design experiments.As a classic technology of standard computer simulation,molecular simulation can construct and analyze complex molecular models to study the dynamic processes of molecular motion.However,the simulation results are easy to be affected by human factors.In recent years,the integration of artificial intelligence and molecular simulation has become a new method of drug design research.Artificial intelligence technology uses big data to screen out the corresponding compounds for molecular simulation and feedback on the simulation results to the artificial intelligence system to optimize the artificial neural network.The combination of artificial intelligence and molecular simulation technology improves the efficiency of drug design research,reduces the influence of human factors on simulation results,and increases the credibility of simulation results.In this review,we summarized the progress of artificial intelligence and molecular simulation technology in drug design to provide a reference for the change from computer assisted drug design(CADD)to artificial intelligence-aided drug design(AIDD)in future pharmaceutical development.

Research progress of coarse-grained molecular dynamics in drug carrier materials / 生物医学工程学杂志

As one of the traditional computer simulation techniques, molecular simulation can intuitively display and quantify molecular structure and explain experimental phenomena from the microscopic molecular level. When the simulation system increases, the amount of calculation will also increase, which will cause a great burden on the simulation system. Coarse-grained molecular dynamics is a method of mesoscopic molecular simulation, which can simplify the molecular structure and improve computational efficiency, as a result, coarse-grained molecular dynamics is often used when simulating macromolecular systems such as drug carrier materials. In this article, we reviewed the recent research results of using coarse-grained molecular dynamics to simulate drug carriers, in order to provide a reference for future pharmaceutical preparation research and accelerate the entry of drug research into the era of precision drug design.

Oxidosqualene cyclases in triterpenoids biosynthesis: a review / 生物工程学报

Triterpenoids are one of the most diverse compounds in plant metabolites, and they have a wide variety of physiological activities and are of important economic value. Oxidosqualene cyclases catalyze the cyclization of 2, 3-oxidosqualene to generate different types of sterols and plant triterpenoids, which is of great significance to the structural diversity of natural products. However, the mechanism of the diversified cyclization of 2, 3-oxidosqualene catalyzed by oxidosqualene cyclases remains unclear. This review summarized the research progress of oxidosqualene cyclases from the aspects of catalytic function, molecular evolutionary relationship between genes and proteins, protein structure, molecular simulation and molecular calculations, which may provide a reference for protein engineering and metabolic engineering of triterpene cyclase.

Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The

Molecular docking of various bioactive compounds from essential oil of Trachyaspermum ammi against the fungal enzyme Candidapepsin-1

The bioactive compounds from essential oil of Trachyaspermum ammi using gas chromatography–mass spectrometryand their inhibition potential against the enzyme Candidapepsin-1 were studied. The research work focuses on themolecular simulation of bioactive compounds against the enzyme that acts as a potential drug target and support thedrug discovery process. Candidapepsin-1 has been reported to be the cause for biofilm formation, superficial skininfections, and oral infections. Fifteen active compounds and their interactions with Candidapepsin-1 were studiedin this research work. The compounds satisfied Lipinski’s rule of five in order to be used as an oral drug. ADMETproperties of the compounds used to determine pharmacodynamic and pharmacokinetic properties which werereported in the study. The compounds were docked against the enzyme with the help of AutoDock 4.2.6 software.Ligustilide has the lowest free binding energy of −5.75 kcal/mol against the Candidapepsin-1 with three hydrogenbond interactions at Ile 223, Tyr 225, and Thr 222 at the active site of the enzyme followed by cedrane with −5.20kcal/mol. The hydrogen bond interactions, Vander Waals interactions, and two-dimensional and three-dimensionalinteractions were studied.

Computational analysis of structure-activity relationship of industrial enzymes / 生物工程学报

Industrial enzymes have become the core "chip" for bio-manufacturing technology. Design and development of novel and efficient enzymes is the key to the development of industrial biotechnology. The scientific basis for the innovative design of industrial catalysts is an in-depth analysis of the structure-activity relationship between enzymes and substrates, as well as their regulatory mechanisms. With the development of bioinformatics and computational technology, the catalytic mechanism of the enzyme can be solved by various calculation methods. Subsequently, the specific regions of the structure can be rationally reconstructed to improve the catalytic performance, which will further promote the industrial application of the target enzyme. Computational simulation and rational design based on the analysis of the structure-activity relationship have become the crucial technology for the preparation of high-efficiency industrial enzymes. This review provides a brief introduction and discussion on various calculation methods and design strategies as well as future trends.

Research advances in immune evasion mechanism of helminths / 中国人兽共患病学报

Helminth infection can lead to organic,digestive and other tissue's pathological damage.Helminth diseases are harmful to human and animal health,and can cause reproductive failure,inhibits the growth and development of juvenile ani-mals,even lead to death of humans and animals in serious cases,and poses significant impacts on public health and causes eco-nomic losses to the animal husbandry.Currently,the prevention and control of helminth disease is largely dependent on inte-grated control measures including the use of drugs.Due to drug residues,drug resistance,and other issues,the development of new drugs and vaccines is imminent.So far,there is few ideal vaccines to control helminth diseases,which is due to that hel-minths have evolved mechanisms to evade host immune attacks during evolution,such as immune isolation,antigen variation, molecular simulation and so on.Therefore,this review describes the recent research advances in the immune evasion strategies of parasitic helminth,which aims to provide a reference for the development of new vaccines or drugs for better prevention and control of helminth diseases.

Preparation and Evaluation of Kaempferol Molecularly Imprinted Monolithic Column with MolecularSimulation-Living Radical Polymerization / 分析化学

Molecular simulation was used to study the interaction between template molecule and functional monomer to shorten the optimization time for the functional monomer and the ratio of functional monomer and template molecule.Kaempferol molecularly imprinted polymerization (MIP) monolithic column was therefore synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization with dibenzyltrithiocarbonate (DBTTC) and ethyleneglycoldim ethacrylate (EDMA) as RAFT and cross-linking agent, respectively, whereas methacrylic acid (MAA) was the optimal functional monomer with the molar ratio of kaempferol/MAA of 1∶4 from molecular simulation results.The results indicate that molecular simulation is useful to simplify the experimental procedure, and DBTTC as RAFT agent can provide more adjustable and better MIP monolithic column.

Inclusion Complex of SBE7-β-CD with TMP: Preparation, Characterization and Molecular Simulation / 中国药学杂志

OBJECTIVE: To prepare inclusion complex of SBE7-β-CD with trimethoprim(TMP) and optimize the preparation process, to evaluate the products by structural characterization and molecular simulation. METHODS: The TMP/SBE7-β-CD inclusion complex was prepared by the ultrasound-freeze-dry method and the preparation process was optimized by Box-Behnken Design-response surface method(BBD-RSM). Inclusion complex was characterized by FT-IR, DSC, XRPD and 1H-NMR. Molecular docking method was used to simulate 3-dimensional conformations of the inclusion complex and the binding energy was calculated. The dissolution and stability were tested. RESULTS: The optimum conditions of TMP/SBE7-β-CD inclusion complex were: temperature(52 ℃), time(45 min), and the ratio of SBE7-β-CD and TMP(mol/mol, 1.7∶1). All characterizations(FT-IR, DSC, XRPD and 1H-NMR) indicated the formation of TMP/SBE7-β-CD inclusion complex. The best 3-dimensional docking conformation was consistent with the characterizations, and the binding energy was -9.015 kcal·mol-1. The TMP dissolution rate of the inclusion complex increased significantly, the hygroscopicity is strong. CONCLUSION: The preparation process of TMP/SBE7-β-CD inclusion complex optimized by BBD-RSM is reasonable and feasible. The characterizations of inclusion complex are reliable. The molecular simulation is corresponded to the characterized results and provided reliable theoretical basis for inclusion experiments.

Docking and ADME/T analysis of silibinin as a potential inhibitor of EGFR kinase for ovarian cancer therapy.

Epidermal Growth Factor Receptor (EGFR) is mostly deregulated and over expressed in ovarian cancer, which is directly linked with STAT3 activation that leads to the accumulation of anti-apoptotoc events and thus, platinum drug resistance occurs. Regarding this, increasing of platinum drug sensitivity by targeting EGFR receptor along with platinum drugs is one of the major strategies in ovarian cancer treatment. In this context, using molecular simulation studies, the present study described the structural and functional properties of silibinin as a potential inhibitor of EGFR tyrosine kinase, and also its metabolic profile had been investigated by SOM prognosis. According to the results, silibinin have shown the significant binding energy by interacting with important residues in the active site. Again, it also processed medium absorption profile with no Fe accessibility. Furthermore, the study is also useful for further clinical based studies and also for the validation of toxicological and pharmacokinetic study.

In silico analysis of indole-3-carbinol and its metabolite DIM as EGFR tyrosine kinase inhibitors in platinum resistant ovarian cancer vis a vis ADME/T property analysis.

Epidermal Growth Factor Receptor (EGFR) is one of the four members of the Human Epidermal Receptor (HER) family, which is deregulated and over expressed in platinum resistant ovarian cancer. Thus, targeting EGFR receptor along with platinum drugs is one of the major strategies to increase the platinum drug sensitivity. That‟s why, in this study, we aimed to investigate the inhibitory activity and binding site analysis of indole-3-carbinol and its active metabolite 3,3'-diindolylmethane by using molecular simulation studies, also metabolic profile had been investigated by SOM prediction. The 3,3'-diindolylmethane showed significant inhibitory activity and binding energy comparing to indole-3-carbinol, also it processed lower toxicity and will undergo aromatic hydroxylation due its high intrinsic activity and Fe accessibility. Though our research study supports previous reports of EGFR inhibition, further in vivo study is necessary for validation of toxicological and pharmacokinetic study. However, the current work tries to address most of the variables in the dynamic drug design process by In silico study in order to boost the potentiality of the selected molecule to serve as good leads in terms of optimum pharmacokinetic and toxicological attributes.

Interaction and Molecular Simulation between Gossypol and Human Serum Albumin / 中国药师

Objective:To explore the interaction between gossypol and human serum albumin ( HSA) . Methods:The interaction of gossypol and HSA under physiological conditions was studied by fluorescence spectroscopy, and the molecular docking software was used to simulate the interaction. Results:The binding constant of gossypol and HSA at 293K and 303K was 2. 390 6 × 105 L·mol-1 and 3. 576 8 × 103 L·mol-1 , respectively. There was one binding site on HSA for gossypol. Hydrogen bond and Van Der Waals inter-actions were involved in the binding process. The binding of gossypol and HAS was closer to tyrosine residue in HSA. The molecular simulation analysis verified the above results. Conclusion: The gossypol-induced fluorescence quenching of HSA belongs to a static quenching procedure.

Binding mechanism between bovine serum albumin and echinacoside / 中草药

Objective: To explore the binding mechanism between echinacoside (ECH) and serum albumin (SA). Methods: The binding parameters were detected by spectrum experiment under physiological conditions, and the molecular modeling techniques had been used to investigate the binding mechanism between ECH and bovine serum albumin (BSA). Results: Molecular docking revealed that ECH binded to BSA mainly by hydrogen bonds and van der Waals forces, and there was a hydrophobic interaction. The results from spectroscopy indicated that the drug could bind with BSA to form static complex with significantly strong bond. The value of binding distances (r) was low, which indicated the occurrence of energy transfer. ECH affected the conformation of micro-domain and changed the hydrophobicity of the binding domain. The fluorescence phase diagram revealed that the changes on the conformational pattern of proteins had been affected by drug conformed to the "all-or-none" pattern. According to the obtained thermodynamic parameters, it also showed that the main interactional force of ECH binding with BSA was hydrogen bonds and van der Waals forces. The fluorescence polarization proved quantitatively that ECH-BSA generated a non-covalent complex. Conclusion: The experimental results agree with computer molecular modeling, which provides helpful reference for the interaction mechanism of ECH binding with BSA.

Nanoinformatics: an emerging area of information technology at the intersection of bioinformatics, computational chemistry and nanobiotechnology

After the progress made during the genomics era, bioinformatics was tasked with supporting the flow of information generated by nanobiotechnology efforts. This challenge requires adapting classical bioinformatic and computational chemistry tools to store, standardize, analyze, and visualize nanobiotechnological information. Thus, old and new bioinformatic and computational chemistry tools have been merged into a new sub-discipline: nanoinformatics. This review takes a second look at the development of this new and exciting area as seen from the perspective of the evolution of nanobiotechnology applied to the life sciences. The knowledge obtained at the nano-scale level implies answers to new questions and the development of new concepts in different fields. The rapid convergence of technologies around nanobiotechnologies has spun off collaborative networks and web platforms created for sharing and discussing the knowledge generated in nanobiotechnology. The implementation of new database schemes suitable for storage, processing and integrating physical, chemical, and biological properties of nanoparticles will be a key element in achieving the promises in this convergent field. In this work, we will review some applications of nanobiotechnology to life sciences in generating new requirements for diverse scientific fields, such as bioinformatics and computational chemistry.