Criteria for Engineering Cutinases: Bioinformatics Analysis of Catalophores

Cutinases are bacterial and fungal enzymes that catalyze the hydrolysis of natural cutin, a three-dimensional inter-esterified polyester with epoxy-hydroxy fatty acids with chain lengths between 16 and 18 carbon atoms. Due to their ability to accept long chain substrates, cutinases are also effective in catalyzing in vitro both the degradation and synthesis of several synthetic polyesters and polyamides. Here, we present a bioinformatics study that intends to correlate the structural features of cutinases with their catalytic properties to provide rational basis for their effective exploitation, particularly in polymer synthesis and biodegradation. The bioinformatics study used the BioGPS method (Global Positioning System in Biological Space) that computed molecular descriptors based on Molecular Interaction Fields (MIFs) described in the GRID force field. The information was used to generate catalophores, spatial representations of the ability of each enzymatic active site to establish hydrophobic and electrostatic interactions. These tools were exploited for comparing cutinases to other serine-hydrolases enzymes, namely lipases, esterases, amidases and proteases, and for highlighting differences and similarities that might guide rational engineering strategies. Structural features of cutinases with their catalytic properties were correlated. The \u201ccatalophore\u201d of cutinases indicate shared features with lipases and esterases

Numerical Model and Experimental Analysis of the Thermal Behavior of Electric Radiant Heating Panels

Electric radiant heating panels are frequently selected during the design phase of residential and industrial heating systems, especially for retrofit of existing buildings, as an alternative to other common heating systems, such as radiators or air conditioners. The possibility of saving living and working space and the ease of installation are the main advantages of electric radiant solutions. This paper investigates the thermal performance of a typical electric radiant panel. A climatic room was equipped with temperature sensors and heat flow meters to perform a steady state experimental analysis. For the dynamic behavior, a mathematical model was created and compared to a thermographic measurement procedure. The results showed for the steady state an efficiency of energy transformation close to one, while in a transient thermal regime the time constant to reach the steady state condition was slightly faster than the typical ones of hydronic systems

Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: preliminary data and computational analysis

This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 \u3bcg/mL (0.37-0.75 \u3bcM) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans

Computational Evolution Protocol for Peptide Design

Computational peptide design is useful for therapeutics, diagnostics, and vaccine development. To select the most promising peptide candidates, the key is describing accurately the peptide-target interactions at the molecular level. We here review a computational peptide design protocol whose key feature is the use of all-atom explicit solvent molecular dynamics for describing the different peptide-target complexes explored during the optimization. We describe the milestones behind the development of this protocol, which is now implemented in an open-source code called PARCE. We provide a basic tutorial to run the code for an antibody fragment design example. Finally, we describe three additional applications of the method to design peptides for different targets, illustrating the broad scope of the proposed approach