Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

Understanding the concepts of community phylogenetics

Background: Community phylogenetics is an emerging field of research that has made important contributions to understanding community assembly. The rapid development of this field can be attributed to the merging of phylogenetics and community ecology research to provide improved clarity on the processes that govern community structure and composition. Question: What are the major challenges that impede the sound interpretation of the patterns and processes of phylogenetic community assembly? Methods: We use four scenarios to illustrate explicitly how the phylogenetic structure of communities can exist in stable or transient phases, based on the different combinations of phylogenetic relationships and phenotypic traits among co-occurring species. We discuss these phases by implicating a two-way process in the assembly and disintegration of the given ecological community. Conclusions: This paper synthesizes the major concepts of community phylogenetics using habitat filtering and competition processes to elucidate how the understanding of phylogenetic community structure is currently hindered by the dynamics of community assembly and disassembly.

Let's talk: how communication affects contract design

We study experimentally how the ability to communicate affects the frequency and effectiveness of flexible and inflexible contracts in a bilateral trade context where sellers can adjust trade quality after observing a post-contractual cost shock and a discretionary buyer transfer. In the absence of communication, we find that rigid contracts are more frequent and lead to higher earnings for both buyer and seller. By contrast, in the presence of communication, flexible contracts are much more frequent and considerably more productive, both for buyers and sellers. Also, both buyer and seller earn considerably more from flexible with communication than rigid without communication. Our results show quite strongly that communication, a normal feature in contracting, can remove the potential cost of flexibility (disagreements caused by conflicting perceptions). We offer an explanation based on social norms.