Figure 10.

Summary of differences in rotamer averaging between complexes of E. coli DHFR. Differences can arise from changes in the extent of rotamer hopping or from changes in local in-well rotamer motions. The corresponding x-ray structure is shown for each complex [E:NADPH (1RX1), E:FOL:NADP⁺ (3QL3), E:MTX:NADPH (1RX3), E:THF:NADP/H (1RX4), E:THF (1RX5), E:FOL (1RX7), and N23PP/S148A E:FOL:NADP⁺ (3QL0)^3,23]. Spheres are shown for Ile, Thr, Val, Leu, and aromatic residues. Ligands are shown as sticks with FOL/THF in yellow and NADP/H in orange. A. The difference in p_major between the given complex and the next complex in the enzymatic cycle is shown for the residues that show variable averaging between complexes (green residues in Figure 9). Side chains with the same rotamer averaging are shown in white, residues with more (less) rotamer averaging than the next complex in the cycle are shown as red (blue), with more red or blue coloring indicating a larger population difference. B. Difference in rotamer averaging between E:MTX:NADPH and E:FOL:NADP⁺ complexes. C. Difference in rotamer averaging between N23PP/S148A and wild type E:FOL:NADP⁺ complexes. D. Difference in rotamer averaging between E:FOL and E:THF. A–D Leu62, Ile94, and Val119 have a different major rotamer depending on the complex, so differences in rotamer averaging are given with respect to the 180° χ₂, +60o χ₁ and −60° χ₁ rotamers, respectively. The color gradient in panels A–D runs from Δp_major = −0.5 (blue) < 0 (white) < 0.5 (red), where Δp_major is the difference in major rotamer population between the displayed complex and the next complex in the catalytic cycle (A) or the complex indicated in parentheses (B–D).