Proteolytic processing of Gag and Gag-Pol polyproteins by the viral protease (PR) is crucial for production infectious HIV-1, inhibitors PR are an integral part current antiretroviral therapy. The process has several layers complexity (multiple cleavage sites substrates; multiple enzyme forms; auto-processing), which calls a systems level approach to identify key vulnerabilities optimal treatment strategies. Here we present first full reaction kinetics model proteolytic HIV-1 PR, taking into...

Abstract In this study, we propose a two-phase scenario for the origin of first protocellular form life, linking two RNA-world models by an explicit dynamical interface that simulates transition metabolically cooperating RNA-replicator community from mineral surface into population membrane vesicles. The agent-based models: Metabolically Coupled Replicator System (MCRS) and Stochastic Corrector Model (SCM), are built on principles systems chemistry, molecular biology, ecology evolutionary...

The remarkable potential of recent forms life for reliably passing on genetic information through many generations now depends the coordinated action thousands specialized biochemical "machines" (enzymes) that were obviously absent in prebiotic times. Thus question how a complicated system like living cell could have assembled Earth seems puzzling. In seeking scientific explanation one has to search step-by-step evolutionary changes from chemistry emergence first proto-cell.We try sketch...

The coexistence of macromolecular replicators and thus the stability presumed prebiotic replicator communities have been shown to critically depend on spatially constrained catalytic cooperation among RNA-like modular replicators. necessary spatial constraints might supplied by mineral surfaces initially, preceding more effective compartmentalization in membrane vesicles which must a later development chemical evolution.Using our surface-bound RNA world model - Metabolic Replicator Model...

The chemical machinery of life must have been catalytic from the outset. Models origins attempted to explain ecological mechanisms maintaining a minimum necessary diversity prebiotic replicator enzymes, but little attention has paid so far evolutionary initiation that diversity. We propose possible first step in this direction: based on our previous model surface-bound metabolic system we try how adaptive specialization enzymatic populations might led more diverse and efficient communities...

Abstract The robust coevolution of catalytically active, metabolically cooperating prebiotic RNA replicators were investigated using an World model the origin life based on physically and chemically plausible first principles. Metabolically Coupled Replicator System assumes to supply essential catalytic activities indispensable produce nucleotide monomers for their own template replication. Using external chemicals as resource necessary ribozyme activities, Watson-Crick type replication...

The RNA World hypothesis offers a plausible bridge from no-life to life on prebiotic Earth, by assuming that RNA, the only known molecule type capable of playing genetic and catalytic roles at same time, could have been first evolvable entity evolutionary path living cell. We developed Metabolically Coupled Replicator System (MCRS), spatially explicit simulation modelling approach RNA-World evolution mineral surfaces, in which we incorporate most important experimental facts theoretical...

A theoretical formulation for complete heteropolymer degradation is developed in terms of Michaelis-Menten reaction kinetics under the quasi-steady-state approximation. This allows concentration entire intermediate decomposition cascade to be accounted as well each species emerging final product. The implemented computationally and results stable across a range orders magnitude K(M) k(cat). model compared with experiment, specifically vitro HIV-1 protease-catalyzed retroviral Gag-polyprotein...

RNA or RNA-like polymers are the most likely candidates for having played lead roles on stage of origin life. is known to feature two three essential functions living entities (metabolism, heredity and membrane): it capable unlimited has a proven capacity catalysing very different chemical reactions which may form simple metabolic networks. The Metabolically Coupled Replicator System class simulation models built these show that an World scenario life ecologically feasible, provided mineral...

The Metabolically Coupled Replicator System (MCRS) model of early chemical evolution offers a plausible and efficient mechanism for the self-assembly maintenance prebiotic RNA replicator communities, likely predecessors all life forms on Earth. MCRS can keep different species together due to their mandatory metabolic cooperation limited mobility mineral surfaces, catalysing reaction steps coherent network that produces own monomers from externally supplied compounds. complexity engine be...

Biological reproduction rests ultimately on chemical autocatalysis. Autocatalytic cycles are thought to have played an important role in the complexification en route life. There two, related issues: what transformations allow such form, and at speed they operating. Here we investigate latter question for solitary as well competitive autocatalytic resource-unlimited batch resource-limited chemostat systems. The of growth tends decrease with length a cycle. Reversibility reproductive step...

Abstract Expertise in science, particularly animal behaviour, may provide people with the capacity to better judgments contrast lay people. Here we explore whether experts a more objective, accurate and coherent evaluation of recently reported anecdote on Atlantic puffin ( Fratercula arctica ) “tool use” (recorded video) which was published major scientific journal but received some scepticism. We relied citizen science developed questionnaire measure ethology ornithology agree or disagree...