The interactions of neutral aromatic ligands with cationic arginine, histidine and lysine amino acid residues have been studied with ab initio calculations, symmetry adapted perturbation theory (SAPT), and a systematic meta-analysis of X-ray structures.

Abstractβ‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required.

Histone lysine methylation is regulated by N-methyltransferases, demethylases, and N-methyl lysine binding proteins. Thermodynamic, catalytic and computational studies were carried out to investigate the interaction of three epigenetic protein classes with synthetic histone substrates containing l- and d-lysine residues. The results reveal that out of the three classes, N-methyl lysine binding proteins are superior in accepting lysines with the d-configuration.

Histone N-lysine methylation is a widespread posttranslational modification that is specifically recognised by a diverse class of N-methyllysine binding reader proteins. Combined thermodynamic data, molecular dynamics simulations, and quantum chemical studies reveal that reader proteins efficiently bind trimethylornithine and trimethylhomolysine, the simplest N-trimethyllysine analogues that differ in the length of the side chain.

Enzymes often use nucleophilic serine, threonine, and cysteine residues to achieve the same type of reaction; the underlying reasons for this are not understood. While bacterial d,d ‐transpeptidases (penicillin‐binding proteins) employ a nucleophilic serine, l,d ‐transpeptidases use a nucleophilic cysteine. The covalent complexes formed by l,d ‐transpeptidases with some β‐lactam antibiotics undergo non‐hydrolytic fragmentation. This is not usually observed for penicillin‐binding proteins, or for the related serine β‐lactamases. Replacement of the nucleophilic serine of serine β‐lactamases with cysteine yields enzymes which fragment β‐lactams via a similar mechanism as the l,d ‐transpeptidases, implying the different reaction outcomes are principally due to the formation of thioester versus ester intermediates. The results highlight fundamental differences in the reactivity of nucleophilic serine and cysteine enzymes, and imply new possibilities for the inhibition of nucleophilic enzymes.

CREBBP bromodomains, epigenetic "reader" proteins that recognize acetylated histone lysine residues, are a current target for cancer therapy. We show that experimental CREBBP binding affinities of small-molecules with aromatic or heteroaromatic functional groups are strongly influenced by a cation-π interaction with a positively charged arginine residue. For a series of fifteen 5-isoxazolylbenzimidazole derivatives, the strength of this non-covalent interaction is directly related to improvements in binding to CREBBP. The aromatic substituents' inductive and resonance effects are not obviously correlated with observed structure and affinity relationships. In contrast, a coulombic electrostatic model can quantitatively predict the interaction strength. We have assessed different Molecular Mechanics (MM) and Quantum Mechanics (QM) descriptions of the protein-ligand interaction. Quantitative models for binding affinity were generated from: (1) Poisson Boltzmann Surface Area (MM-PBSA) and Generalized Born Surface Area (MM-GBSA) scoring functions that incorporated the entire ligand and (2) QM-complexation energies and (3) Electrostatic Potential Surface values (ESPs) that analyzed the varying aromatic group. A linear relationship between QM-computed ESP values is established for the cation-π interaction strength, and gives the best correlation (R = 0.84) with experimental binding affinities. This model also ranks ligand affinity most accurately (r = 0.91) from the models tested. Consideration of the electrostatic potential in response to the local effects of substituents in addition to that of the aromatic ring is necessary to understand and describe the interaction with the cationic guanidinium ion. This leads to an improved understanding and the ability to quantitatively predict the magnitude of non-covalent interactions in the CREBBP active site.

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Today there is an increasing need for assistive technology to help people with disabilities to attain some level of autonomy in terms of communication and movement. People with disabilities, especially total paralysis is often unable to use the biological communication channels such as voice and gestures hence digital communication channels are required. Research on Human Computer Interaction (HCI) is striving to help such individuals to convert human intentions into control signals to operate devices. The technique of measuring cornea retinal potential associated with eye movement is called Electrooculography. Eye movements are behaviors that can be measured and their measurements provide the sensitive means of learning about cognitive and visual stimuli. A human eye conveys a great deal of information with regards to the direction of the eye movements. Further, the direction in which an individual is looking shows where his or her attention is focused. Eye movements are naturally divided into three categories one is the saccades in which eyes quickly change the point of fixation and another is a smooth pursuit movement in which eyes to closely follow a moving object at a steady coordinated velocity, rather than in saccades and the other is a vergence movement in which eye rotates in the opposite direction. By tracking the position of the eye movement useful interfaces can be developed that permit the user to commune and control in a more general way. This paper convey some basic idea about various feature extraction techniques and classification techniques used to categorize the eye movement tasks and also it gives a vision on different issues associated in the field of Electrooculography based Human Computer Interface.