In silico analysis of metal coordination geometry in arsenic, beryllium, and lead bound structures

Abstract

Metal toxicity is a potential hazard to health and toxic effects of metals have been implicated in many diseases. Understanding the interaction of toxic metals becomes vital to prevent hazards following its association in living systems. Coordination chemistry helps in predicting the metal environments like coordinating residues, coordination space, metal coordination geometry, etc. Our work aimed at predicting the coordination of toxic metals arsenic, lead, and beryllium. In this work, we analyzed coordination for each metal from a set of arsenic, beryllium and lead bound structures which were retrieved from the Protein Data Bank. The structures were validated using B-factor and occupancy of the coordinating residues towards the metals. Coordination patterns such as chelate residues, chelate length, geometry, coordination number and structural architecture were predicted. Coordination geometry of the metals was exposed beyond the coordination space with their coordination number ranging from 2 to 11. Analysis of metal environment revealed the acidic amino acids aspartic acid, glutamic acid, and the basic amino acids lysine, histidine, and cysteine to be predominant in coordinating with the metals. Chelate patterns like DDVMITAK, DWNVTVK, ESGKNSS for beryllium, CCCSK, DSDWD for lead and FLICVI and LKHHKEE for arsenic were predicted to be common through extended coordination space. The distinct molecular geometries such as pentagonal bipyramid and square planar were observed only in lead bound structures but not in beryllium and arsenic bound structures. Beryllium had a larger influence than arsenic and lead, based on conformational changes owing to the presence of the metals. Our coordination study puts forth several propositions based on the metal environment that would help in designing chelation strategies.

Graphical Abstract

Keywords:

• Coordination geometry
• Beryllium
• Lead
• Arsenic
• Chelate

Acknowledgements

The authors thank the management of the VIT University for providing the facilities and encouragement to carry out this work. The authors also thank the editor and anonymous reviewers for their valuable comments and suggestions that helped to strengthen the quality of the work.