Solid-state NMR (SSNMR) has gained importance as a versatile tool to elucidate the structure and function of many chemical and biological molecules. In this thesis, we have used SSNMR to study the interactions of an antimicrobial peptide (AMP), Protegrin-1 (PG-1) with membranes of varying lipid composition. Based on our studies we have proposed a model for the mechanism of action of PG-1 with two different lipid membranes. PG-1 is a disulfide-linked beta-sheet peptide with broad-spectrum antimicrobial activities. Similar to many AMPs, it selectively disrupts the anionic membranes of microbial cells but leaves the cholesterol-rich zwitterionic mammalian cell membranes intact.;Studying the origin of membrane selectivity and elucidating the quaternary structure of PG-1 and its dependence on the lipid environment is important for understanding its structure-function relation. 31P spectra of oriented lipid bilayers are a very good indicator of the membrane order and we have used this feature to explain the origin of membrane selectivity of PG-1. We have found that the presence of anionic lipids facilitates PG-1 disruption while the presence of cholesterol protects the membrane from PG-1 activity. Rotation-echo double-resonance (REDOR) is a well-established technique to determine heteronuclear distances in solids. We have used 1H{lcub} 13C{rcub} and 13C{lcub}19F{rcub} REDOR to determine the intermolecular packing of PG-1. Measured intermolecular distances show that PG-1 hairpins pack in a parallel fashion in POPC membranes, with the C-terminal strands facing each other.;To investigate whether oligomerization underlies the membrane selectivity, we have determined the oligomeric state of PG-1 and measured its depth of insertion in the anionic and zwitterionic lipid membranes using centerband-only detection of exchange (CODEX) and 1H spin diffusion techniques. 19F CODEX experiments indicate that PG-1 exists as (NCCN)n multimers in both the lipid membranes. 1H spin diffusion experiment shows that these PG-1 multimers are membrane inserted in bacterial-mimetic membranes while in mammalian-mimetic systems they are surface bound. Results obtained from CODEX and spin diffusion experiments suggest that whereas PG-1 forms transmembrane pore in anionic membranes, it exists as beta-sheet on the membrane surface in cholesterol-containing membranes. Thus the oligomeric structure and depth of insertion differ with membrane composition and this helps to explain the basis of selectivity exhibited by PG-1.;Antimicrobial activity of the AMPs depend on various factors such as charge, amphipathicity and conformation of the peptide. Understanding the structure-function relationship of these AMPs is essential to develop a potent antibiotic that is capable of destroying bacterial cells without affecting the host cell membranes. These mutations can change the conformation and other important features which results in altering the membranolytic property of the peptide. The disulfide bonds are known to be important for the antimicrobial activity of PG-1 but the underlying structural reasons are not well understood. We have used SSNMR techniques to study the membrane-bound conformation, dynamics and topology of a disulfide-deleted analog of PG-1 where the Cys residues are replaced by Ala.;Multiple residues were uniformly 13C labeled to measure their chemical shifts, which are excellent indicators of protein conformation. 1D and 2D correlation experiments were conducted to obtain the 13C resonance assignments. The secondary structure of disulfide-deleted PG-1 (Ala-PG1) is a random coil in solution while in the membrane-bound state it exhibits two conformations: a highly mobile random coil and a rigid beta-sheet structure. 1H spin diffusion experiments show that the beta-sheet form of Ala-PG1 inserts into the anionic lipid bilayer while it is surface bound in cholesterol-containing lipid bilayers. The removal of disulfide bonds results in a fraction of the molecule existing as random coils that are loosely bound to the membrane while others retain the beta-sheet form and have similar membrane binding topology as the wild type PG-1. The reduced potency of Ala-PG1 can therefore be attributed to the decrease in the membrane active membrane inserted beta-sheet form of the peptide. Thus using SSNMR we have investigated the peptide-lipid interactions of PG-1 and its mutant and have correlated its structure function abilities.