Molecular dynamics modeling the synthetic and biological polymers interactions pre-studied via docking

Abstract

In previous works we reported the design, synthesis and in vitro evaluations of synthetic anionic polymers modified by alicyclic pendant groups (hydrophobic anchors), as a novel class of inhibitors of the human immunodeficiency virus type 1 (HIV-1) entry into human cells. Recently, these synthetic polymers interactions with key mediator of HIV-1 entry-fusion, the tri-helix core of the first heptad repeat regions [HR1]3 of viral envelope protein gp41, were pre-studied via docking in terms of newly formulated algorithm for stepwise approximation from fragments of polymeric backbone and side-group models toward real polymeric chains. In the present article the docking results were verified under molecular dynamics (MD) modeling. In contrast with limited capabilities of the docking, the MD allowed of using much more large models of the polymeric ligands, considering flexibility of both ligand and target simultaneously. Among the synthesized polymers the dinorbornen anchors containing alternating copolymers of maleic acid were selected as the most representative ligands (possessing the top anti-HIV activity in vitro in correlation with the highest binding energy in the docking). To verify the probability of binding of the polymers with the [HR1]3 in the sites defined via docking, various starting positions of polymer chains were tried. The MD simulations confirmed the main docking-predicted priority for binding sites, and possibilities for axial and belting modes of the ligands–target interactions. Some newly MD-discovered aspects of the ligand’s backbone and anchor units dynamic cooperation in binding the viral target clarify mechanisms of the synthetic polymers anti-HIV activity and drug resistance prevention.Electronic supplementary materialThe online version of this article (doi:10.1007/s10822-014-9749-8) contains supplementary material, which is available to authorized users.

How to Fight Kinetics in Complex Radical Polymerization Processes: Theoretical Case Study of Poly(divinyl ether‐alt‐maleic anhydride)

“…with broad spectrum of biomedical applicability . Authors of the paper have their own background in design, synthesis, and development of DVEMAN‐derived inhibitors of HIV, influenza, herpes, and other human viruses …”

“…Yielding FRP products are usually not regulated on the molecular scale, consisting of blocks obtained through the fastest routes of the polymerization their own background in design, synthesis, and development of DVEMAN-derived inhibitors of HIV, influenza, herpes, and other human viruses. [13][14][15][16][17][18][19][20][21][22] Two challenges against active advancement of DVEMANbased products toward a medical practice appeared as typical for synthetic polymers: an accurate control of molar mass distribution with low dispersity and possible irregularity of the polymeric backbone structures.…”

Chirality‐Induced Variation in Interaction of Two Similar Copper(II) Coordination Polymers with Calf Thymus DNA: Exploration of Their Antimicrobial Activity and Cytotoxicity

“…Molecular docking algorithms has emerged as an alternative method to facilitate drug discovery via virtual screening of metal complexes with various viral proliferating and cancer causing proteins ,. Molecular docking determines specific interactions between synthetic and biological polymers, therefore, it is an interesting platform for advancements in modern medicine and pharmacy ,…”

“…[15,16] Molecular docking determines specific interactions between synthetic and biological polymers, therefore, it is an interesting platform for advancements in modern medicine and pharmacy. [17,18] In the present work, we used two tridentate N 2 O donor Schiff bases to prepare two polynuclear dca bridged copper(II) Schiff base complexes. The structures of both complexes were confirmed by spectroscopy and single crystal X-ray crystallography.…”

Modeling and theoretical analysis of ring specific mimicry in view of isomerism within medicinal promising oligomers of "DIVEMA"

“…В нашем конкретном случае детальные знания о составе и молекулярно-структурных особенностях остова ДВЭМА необходимы для адекватного и точного моделирования самих олигомеров ДВЭМА DER и взаимодействий таких лигандов с мишенями. Если ранее [4,20,49,50] 9 в конструкциях моделей ДВЭМА DER и симуляции их взаимодействий с белковыми мишенями вирусов ВИЧ, гриппа и Эбола, мы ограничивались преимущественно "фурановыми" вариантами, то теперь имеем возможность уточнения параметров моделируемых объектов и вычислительных экспериментов с учётом полученных данных (рис. 7).…”