Abstract: Experimental and computational studies have shown that cellular membranes deform to stabilize the inclusion of transmembrane (TM) proteins harboring charge. Recent analysis suggests that membrane bending helps to expose charged and polar residues to the aqueous environment and polar head groups. We previously used elasticity theory to identify membrane distortions that minimize the insertion of charged TM peptides into the membrane. Here, we extend our work to consider the energetics of ion and small peptide penetration into the membrane as well as large protein complexes. First, we show that our continuum method accurately reproduces energy profiles and membrane shapes generated from molecular simulations of bare ion permeation at a fraction of the computational cost. Importantly, we find that the energetics of membrane deformation strongly depend on membrane patch size both for ions and peptides. Finally, we present experimental and theoretical analysis that suggests that the antibacterial protein RegIIIa, a C-type lectin, forms channel like complexes that disrupt cellular homeostasis by inserting into membranes containing anionic lipids. We believe that our work presents a novel, computationally efficient method to simulate the effects of small molecules, peptides and large complexes with the membrane.