A novel approach to accurately determine residue specific noncovalent interaction strengths (zeta) of proteins from NMRmeasured fast side chain motional parameters (O-axis(2)) is presented. By probing the environmental sensitivity of side chain conformational energy surfaces of individual residues of a diverse set of proteins, the microscopic connections between zeta O-axis(2), conformational entropy (S-conf), conformational barriers, and rotamer stabilities established here are found to be universal among proteins. The results reveal that side chain flexibility and conformational entropy of each residue decrease with increasing and that for each residue type there exists a critical range of zeta, determined primarily by the mean side chain conformational barriers, within which flexibility of any residue can be reversibly tuned from highly flexible (with O-axis(2) similar to 0) to highly restricted (with O-axis(2) similar to 1) by increasing zeta by similar to 3 kcal/mol. Beyond this critical range of zeta,both side chain flexibility and conformational entropy are insensitive to zeta. The interrelationships between conformational dynamics, conformational entropy, and "noncovalent interactions of protein side chains established here open up new avenues to probe perturbation-induced (for example, ligandbinding, temperature, pressure) changes in fast side chain dynamics and thermodynamics of proteins by comparing their conformational energy surfaces in the native and perturbed states.