Predicting peak spectral sensitivities of vertebrate cone visual pigments using atomistic molecular simulations

Vision is the dominant sensory modality in many organisms for foraging, predator avoidance, and social behaviors including mate selection. Vertebrate visual perception is initiated when light strikes rod and cone photoreceptors within the neural retina of the eye. Sensitivity to individual colors, i.e., peak spectral sensitivities (λmax) of visual pigments, are a function of the type of chromophore and the amino acid sequence of the associated opsin protein in the photoreceptors. Large differences in peak spectral sensitivities can result from minor differences in amino acid sequence of cone opsins. To determine how minor sequence differences could result in large spectral shifts we selected a spectrally-diverse group of 14 teleost Rh2 cone opsins for which sequences and λmax are experimentally known. Classical molecular dynamics simulations were carried out after embedding chromophore-associated homology structures within explicit bilayers and water. These simulations revealed structural features of visual pigments, particularly within the chromophore, that contributed to diverged spectral sensitivities. Statistical tests performed on all the observed structural parameters associated with the chromophore revealed that a two-term, first-order regression model was sufficient to accurately predict λmax over a range of 452–528 nm. The approach was accurate, efficient and simple in that site-by-site molecular modifications or complex quantum mechanics models were not required to predict λmax. These studies identify structural features associated with the chromophore that may explain diverged spectral sensitivities, and provide a platform for future, functionally predictive opsin modeling.Author summary: Vertebrate color vision is possible when cone visual pigments with distinct peak spectral sensitivities (λmax) are expressed in separate cone populations and provide differential input to downstream neurons. The λmax is a function of the type of chromophore (such as 11-cis retinal) and the amino acid sequence of the associated opsin protein. In this study we utilize a molecular modeling approach to predict with high accuracy the λmax of cone visual pigments, using only the amino acid sequences of the corresponding opsin proteins as input. Such a functionally predictive, genome to phenome, opsin modeling has been elusive for decades, and now carries high potential for future applications in evolutionary biology, biophysics, bio-engineering, and vision science.